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1.

Background

The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis.

Methods

The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping.

Results

Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: P = 0.006, OR = 0.83, 95% CI = 0.72–0.95; CT vs. CC: P = 0.05, OR = 0.83, 95% CI = 0.69–1.00; TT vs. CC: P = 0.05, OR = 0.73, 95% CI = 0.53–1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (P = 0.06, OR = 1.21, 95% CI = 0.99–1.49) and AC vs. AA (P = 0.09, OR = 1.21, 95% CI = 0.97–1.51).

Conclusions

The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.  相似文献   

2.

Background

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis.

Aim

A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome.

Methods

PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment.

Results

Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09–1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13–1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10–1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13–1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60–0.94, p = 0.01).

Conclusion

The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.  相似文献   

3.

Objective

To explore the association between transforming growth factor-beta1 (TGF-β1) T869C polymorphism and risk of ischemic stroke (IS) by performing a meta-analysis based on published articles.

Methods

Systematic electronic searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANFANG Database were performed. The strength of the association was calculated by pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by Begg’s funnel plot and Egger’s test.

Results

A total of 6 studies involving 1701 cases were included. The overall estimates did not show any significant association between TGF-β1 T869C polymorphism and risk of IS under all genetic models (C vs. T: OR = 1.08,95%CI = 0.88–1.32; CC vs. TT:OR = 1.17,95%CI = 0.79–1.72; CT vs. TT: OR = 0.91, 95%CI = 0.68–1.22; CC+CT vs. TT: OR = 0.99, 95%CI = 0.73–1.35; CC vs. CT+TT: OR = 1.23, 95%CI = 0.95–1.59). Similar lacking associations were observed in subgroup analysis based on ethnicity and source of controls. When stratified by study design, significant increased association of IS risk was found in cohort studies under genetic models except recessive model(C vs. T: OR = 1.18, 95%CI = 1.05–1.32; CC vs. TT: OR = 1.40, 95%CI = 1.10–1.77; CT vs. TT: OR = 1.23, 95%CI = 1.02–1.49; CC+CT vs. TT: OR = 1.27, 95%CI = 1.03–1.57; CC vs. CT+TT, OR = 1.21, 95%CI = 0.99–1.47), whereas in case-control studies a significant decreased risk was detected under heterozygote comparison(CT vs. CC: OR = 0.72, 95%CI = 0.57–0.92). However, after correction for multiple testing, the associations were observed to be null significant in both cohort and case-control subgroups among all genetic models.

Conclusion

This meta-analysis suggested that current epidemiological studies of TGF-β1 T869C polymorphism are too inconsistent to draw a conclusion on the association with IS susceptibility. Given the small sample size and remarkable between-study heterogeneity, further well-designed prospective large-scale studies are warranted.  相似文献   

4.

Background

Accumulating evidence has suggested that Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism might be related to cancer risk. However, epidemiologic findings have been inconsistent. We therefore performed a meta-analysis to clarify the association between the SMAD7 rs12953717 polymorphism and cancer risk.

Methods

A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and cancer risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results

A total of 14 case-control studies, including 16928 cases and 14781 controls, were included in the present meta-analysis. The overall results showed that the variant genotypes were associated with a significantly increased risk of all cancer types (homozygote comparison, OR = 1.23, 95%CI = 1.10–1.38, P<0.01; heterozygote comparison, OR = 1.12, 95%CI = 1.02–1.22, P = 0.02; recessive model, OR = 1.17, 95%CI = 1.07–1.29, P<0.01; dominant model, OR = 1.15, 95%CI = 1.06–1.25, P<0.01; allelic model, OR = 1.12, 95%CI = 1.06–1.18, P<0.01). Further sensitivity analysis confirmed the significant association. In the subgroup analysis by ethnicity, SMAD7 rs12953717 polymorphism was significantly associated with cancer risk in both Caucasians and Asians. In the subgroup analysis by cancer types, SMAD7 rs12953717 polymorphism was significantly associated with colorectal cancer.

Conclusions

Our investigations demonstrate that rs12953717 polymorphism is associated with the susceptibility of cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.  相似文献   

5.

Background

The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a very important role in DNA double-strand break repair (DSBR). Variations in the XRCC3 gene might lead to altered protein structure or function which may change DSBR efficiency and result in cancer. The XRCC3 C18067T polymorphism has been reported to be associated with skin cancer susceptibility, yet the results of these previous results have been inconsistent or controversial. To derive a more precise estimation of the association, we conducted a meta-analysis.

Methods

The quality of the studies was assessed according to a predefined scale. The association between the XRCC3 C18067T polymorphism and skin cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).

Results

Overall, no significant association was observed between XRCC3 C18067T polymorphism and skin cancer risk in any genetic model. Stratified analyses according to tumor type, significant association was found in the relationship between XRCC3 C18067T polymorphism and nonmelanoma skin cancer risk (homozygote comparison TT versus CC: OR = 0.74, 95%CI = 0.61–0.90, P = 0.003; recessive model TT versus TC/CC: OR = 0.81, 95%CI = 0.68–0.95, P = 0.01). Furthermore, significant association was also observed in XRCC3 C18067T polymorphism with both basal cell carcinoma risk (homozygote comparison TT versus CC: OR = 0.70, 95%CI = 0.53–0.92, P = 0.011; recessive model TT versus. TC/CC: OR = 0.74, 95%CI = 0.60–0.92, P = 0.007) and squamous cell carcinoma risk (heterozygote comparison TT versus .CC: OR = 0.81, 95%CI = 0.67–0.99, P = 0.04; dominant model TT/TC versus .CC: OR = 0.81, 95%CI = 0.68–0.98, P = 0.029).

Conclusion

The present meta-analysis demonstrates that XRCC3 C18067T polymorphism was not associated with risk of cutaneous melanoma but contributed a decreased risk to both basal cell carcinoma and squamous cell carcinoma.  相似文献   

6.

Background

A number of studies have explored the association between methyl enetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to cervical cancer and cervical intraepithelial neoplasia (CIN). However, results remained controversial. To address this gap, we decided to conduct a meta-analysis of all available published studies.

Methods

Electronic literature searches of the PubMed, EmBase and Medline databases were performed up to April 30, 2012. Fixed-effects or random-effects model was used to calculate the pooled ORs for different genetic models.

Results

A total of 12 case-control studies were ultimately identified. No statistical correlation was found between C677T variants and cervical cancer for the overall population. However, subgroup analyses on the White women pointed to a significant protective effect for individuals heterozygous or homozygous for the T-allele (for CT vs. CC: OR = 0.72, 95% CI 0.59–0.88; for TT vs. CC: OR = 0.69, 95% CI = 0.49–0.97; for CT+TT vs. CC: OR = 0.71, 95% CI 0.59–0.86). C677T variants were associated with neither combined nor stratified CIN among the overall population.

Conclusions

This meta-analysis suggests that White women with mutant C677T genotypes might have a lower risk of cervical cancer, yet lacking enough statistical robustness. Further investigations are needed to get more insight into the role of this polymorphism in cervical carcinogenesis.  相似文献   

7.

Background

Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the pathogenesis of lung cancer by altering the expression of tumor-related microRNAs. Several studies were investigated in recent years to evaluate the association between hsa-miR-196a2 rs11614913 polymorphism and increased/decreased lung cancer risk. In the present study, we performed a meta-analysis to systematically summarize the possible association.

Methodology/Principal Findings

We performed a meta-analysis of 4 case-control studies that included 2219 lung-cancer cases and 2232 cancer-free controls. We evaluated the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In the overall analysis, it was found that the rs11614913 polymorphism significantly elevated the risk of lung cancer (CC versus (vs.) TT OR = 1.26, 95% CI 1.07–1.49, P = 0.007; CC/CT vs. TT: OR = 1.13, 95% CI 0.98–1.29, P = 0.007; C vs. T: OR = 1.12, 95% CI 1.03–1.22, P = 0.008). In the subgroup analysis by ethnicity, statistically significantly increased cancer risk was found among Asians (CC vs. TT: OR = 1.30, 95% CI 1.10–1.54, P = 0.003; CT vs. TT: OR = 1.16, 95% CI 1.01–1.34, P = 0.039; CC vs. CT/TT: OR = 1.21, 95% CI 1.04–1.41, P = 0.012; C vs. T: OR = 1.14, 95% CI 1.05–1.25, P = 0.002). For Europeans, a significant association with lung cancer risk was found in recessive model (CC vs. CT/TT: OR = 0.63, 95% CI 0.40–0.98, P = 0.040). No publication bias was found in this study.

Conclusions/Significance

Our meta-analysis suggests that the rs11614913 polymorphism is significant associated with the increased risk of lung cancer, especially in Asians. Besides, the C allele of rs11614913 polymorphism may contribute to increased lung cancer risk.  相似文献   

8.

Background

To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, and Web of Science databases, we identified outcome data from all articles estimating the association between MTHFR polymorphism and cervical cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 12 studies with 2,924 cases (331 cervical intraepithelial neoplasia (CIN) I, 742 CIN II/III, 1851 invasive cervical cancer) and 2,581 controls were identified. There was no significant association between MTHFR C677T polymorphism and CIN I risk (T vs. C, OR = 1.10, 95% CI = 0.92–1.31; TT vs. CC, OR = 1.14, 95% CI = 0.78–1.68; TT+CT vs. CC, OR = 1.22, 95% CI = 0.94–1.58; TT vs. CT+CC, OR = 0.99, 95% CI = 0.70–1.40). For the CIN II/III, lack of an association was also found (T vs. C, OR = 1.08, 95% CI = 0.95–1.23; TT vs. CC, OR = 1.15, 95% CI = 0.87–1.52; TT+CT vs. CC, OR = 1.13, 95% CI = 0.94–1.35; TT vs. CT+CC, OR = 1.07, 95% CI = 0.83–1.38). The T allele had significant association to susceptibility of invasive cervical cancer in recessive model (TT vs. CT+CC, OR = 1.23, 95% CI = 1.02–1.49). On subgroup analysis by ethnicity, similarly significant differences in T vs. C, TT vs. CC, and recessive model were found in Asians.

Conclusion

The present meta-analysis suggested that MTHFR C677T polymorphism were to substantially contribute to invasive cervical cancer in recessive model.  相似文献   

9.

Background

Though HLA-DP/DQ is regarded to associate with HBV susceptibility and HBV natural clearance, its role in hepatocellular carcinoma (HCC) development is obscure. And the role of STAT4 in HBV susceptibility and clearance as well as HCC development is still contentious. Therefore, we conducted this study, aiming to clarify these obscure relationships.

Methods

We recruited 1312 Chinese Han subjects including healthy controls, HBV carriers and HCC patients in the experiment stage. The meta-analysis included 3467 HCC patients and 5821 HBV carriers to appraise the association with HCC development.

Results

Consistent with previous studies, HLA-DP/DQ associated with HBV susceptibility and HBV natural clearance (p<0.05). However, the experiment showed that HLA-DP rs3077, rs9277535 and rs7453920 did not associate with HCC development (dominant model, rs3077, OR = 0.86, 95%CI = 0.62–1.18; rs9277535, OR = 0.94, 95%CI = 0.68–1.30; rs7453920, OR = 0.75, 95%CI = 0.44–1.27). Meta-analysis again consolidated this conclusion (allele model, rs3077, OR = 0.94, 95%CI = 0.87–1.02; rs9277535, OR = 1.04, 95%CI = 0.97–1.11; rs7453920, OR = 0.89, 95%CI = 0.76–1.02). As for STAT4 rs7574865, we did not find any significant association with HBV susceptibility (OR = 0.91, 95%CI = 0.66–1.26) or HBV natural clearance (OR = 1.13, 95%CI = 0.86–1.49). Moreover, current data failed to acquire positive connection of rs7574865 with HCC development (experiment, OR = 0.86, 95%CI = 0.62–1.19; meta-analysis, OR = 0.87, 95%CI = 0.74–1.03), which may be due to the small sample size.

Conclusions

HLA-DP/DQ polymorphisms (rs3077, rs9277535, rs7453920) did not associate with HCC development, but did correlate with HBV susceptibility and HBV natural clearance. STAT4 rs7574865 seemed not to correlate with HBV susceptibility or natural clearance. And it seemed rather ambiguous in its role on HCC development at present.  相似文献   

10.

Background

Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) and prostate cancer (PCa) risk report conflicting results. To derive a more precise estimation of the relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was performed.

Methodology/Principal Findings

A comprehensive literature search was conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk. A total of 14 independent studies, including 6380 cases and 5807 controls, were identified. We investigated by meta-analysis the effects of 5 polymorphisms in CYP1B1 L432V (12 studies, 5999 cases, 5438 controls), R48G (6 studies, 1647 cases, 1846 controls), N453S (4 studies, 1407 cases, 1499 controls), −13C/T (4 studies, 1116 cases, 1114 controls), and A119S (4 studies, 1057 cases, 1018 controls). There was no evidence that L432V had significant association with PCa in overall population. After subgroup analyses by ethnicity, we found that L432V was significantly associated with PCa risk in Asians (additive: OR = 2.38, 95%CI = 1.31-4.33, P = 0.004; recessive: OR = 2.11, 95%CI = 1.17–3.79, P = 0.01; dominant: OR = 1.52, 95%CI = 1.14–2.01, P = 0.004; allelic: OR = 1.52, 95%CI = 1.20–1.92, P = 0.0006). When stratified by source of controls, significantly elevated PCa risk was found in all genetic models in population based studies (additive: OR = 1.34, 95%CI = 1.14–1.57, P = 0.0003; recessive: OR = 1.25, 95%CI = 1.09–1.43, P = 0.002; dominant: OR = 1.25, 95%CI = 1.11–1.41, P = 0.0002; allelic: OR = 1.18, 95%CI = 1.09–1.28, P<0.0001). For N453S, there was a significant association between N453S polymorphism and PCa risk in both overall population (dominant: OR = 1.18, 95%CI = 1.00–1.38, P = 0.04) and mixed population (domiant: OR = 1.31, 95%CI = 1.06–1.63, P = 0.01; allelic: OR = 1.27, 95%CI = 1.05–1.54, P = 0.01). For A119S, our analysis suggested that A119S was associated with PCa risk under recessive model in overall population (OR = 1.37, 95%CI = 1.04–1.80, P = 0.03).

Conclusions

The results suggest that L432V, N453S, and A119S polymorphisms of CYP1B1 might be associated with the susceptibility of PCa. Further larger and well-designed multicenter studies are warranted to validate these findings.  相似文献   

11.

Background

Recent studies on the association between CD14-159C/T polymorphism and sepsis showed inconclusive results. Accordingly, we conducted a comprehensive literature search and a meta-analysis to determine whether the CD14-159C/T polymorphism conferred susceptibility to sepsis or was associated with increased risk of death from sepsis.

Methodology

Data were collected from the following electronic databases: PubMed, Embase, Medline, Web of Knowledge, and HuGE Navigator, with the last report up to June 15, 2012. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. We summarized the data on the association between CD14-159C/T polymorphism and sepsis in the overall population and subgroup by ethnicity and sepsis subtype.

Principal Findings

A total of 16 studies on sepsis morbidity (1369 cases and 2382 controls) and 4 studies on sepsis mortality (731 sepsis patients) met the inclusion criteria for meta-analysis. Overall analysis showed no strong evidences of association with sepsis susceptibility under any genetic model. However, slight associations were found in Asian populations (dominant model: OR = 1.38, 95%CI = 0.96–1.98, P = 0.08) and septic shock patients (dominant model: OR = 1.72, 95%CI 1.05–2.83, P = 0.03; allelic model: OR = 1.52, 95%CI 1.09–2.12, P = 0.01) in the stratified analysis. Moreover, there was borderline association between CD14-159C/T and sepsis mortality under the dominant genetic model (OR = 1.44, 95%CI = 0.98–2.11, P = 0.06).

Conclusions/Significance

This meta-analysis suggests that the CD14-159C/T polymorphism may not be a significant susceptibility factor in the risk of sepsis and mortality. Only weak associations were observed in Asian populations and septic shock patients. More studies based on larger sample sizes and homogeneous sepsis patients are needed to confirm these findings.  相似文献   

12.

Background

The 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene is considered to have a significant effect on colorectal cancer susceptibility, but the results are inconsistent. In order to investigate the association between the MTHFR 677C>T polymorphism and the risk of colorectal cancer, a meta-analysis was held based on 71 published studies.

Methods

Eligible studies were identified through searching the MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and CNKI database. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with x2-based Q-test. Begg''s and Egger''s test were also carried out to evaluate publication bias. Sensitive and subgroup analysis were also held in this meta-analysis.

Results

Overall, 71 publications including 31,572 cases and 44,066 controls were identified. The MTHFR 677 C>T variant genotypes are significantly associated with increased risk of colorectal cancer. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for CC vs TT (OR = 1.076; 95%CI =  1.008–1.150; I2 = 52.3%), CT vs TT (OR = 1.102; 95%CI = 1.032–1.177; I2 = 51.4%) and dominant model (OR = 1.086; 95%CI = 1.021–1.156; I2 = 53.6%). Asians for CC vs TT (OR  = 1.226; 95%CI  = 1.116–1.346; I2  = 55.3%), CT vs TT (OR  = 1.180; 95%CI  = 1.079–1.291; I2  = 36.2%), recessive (OR  = 1.069; 95%CI  = 1.003-1.140; I2  = 30.9%) and dominant model (OR  = 1.198; 95%CI  = 1.101-1.303; I2  = 52.4%), and Mixed populations for CT vs TT (OR  = 1.142; 95%CI  = 1.005-1.296; I2  = 0.0%). However, no associations were found in Africans for all genetic models.

Conclusion

This meta-analysis suggests that the MTHFR 677C>T polymorphism increases the risk for developing colorectal cancer, while there is no association among Africans found in subgroup analysis by ethnicity.  相似文献   

13.

Background

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs.

Methods

An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis.

Results

A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR  = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR  = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR  = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR  = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls.

Conclusion

The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted.  相似文献   

14.

Background

Many studies have investigated the distributions of RANTES genotypes between HIV-1 infected patients and uninfected individuals. However, no definite results have been put forward about whether the RANTES −28C/G polymorphism can affect HIV-1 susceptibility.

Methods

We performed a meta-analysis of 12 studies including 7473 subjects for whom the RANTES −28C/G polymorphism was genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of the polymorphism with HIV-1 susceptibility. By dividing the controls into healthy controls and HIV-1 exposed but seronegative (HESN) controls, we explored the both allelic and dominant genetic models.

Results

By using the healthy controls, we found a marginally significant association between the −28C/G polymorphism and susceptibility to HIV-1 infection in the allelic model (OR = 0.82, 95%CI = 0.70–0.97). But sensitivity analysis suggested that the association was driven by one study. We further performed stratified analysis according to ethnicity. The −28G allele decreased susceptibility to HIV-1 infection in the allelic model among Asians (OR = 0.79, 95%CI = 0.66–0.94). By using the HESN controls, no association between the polymorphism −28C/G and the susceptibility to HIV-1 infection was revealed in either the allelic model (OR = 0.84, 95%CI = 0.60–1.17) or the dominant model (OR = 0.77, 95%CI = 0.54–1.10).

Conclusions

Our findings suggested that the RANTES −28G allele might play a role in resistance to HIV-1 infection among Asians. Additional well-designed studies were required for the validation of this association.  相似文献   

15.

Background

Studies in populations unexposed to folic acid (FA) fortification have demonstrated that MTHFR C677T polymorphism is associated with increased risk of higher grades of cervical intraepithelial neoplasia (CIN 2+). However, it is unknown whether exposure to higher folate as a result of the FA fortification program has altered the association between MTHFR C677T and risk of CIN, or the mechanisms involved with such alterations. The current study investigated the following in a FA fortified population: 1) The association between MTHFR C677T polymorphism and risk of CIN 2+; 2) The modifying effects of plasma folate concentrations on this association; and 3) The modifying effects of plasma folate on the association between the polymorphism and degree of methylation of long interspersed nucleotide elements (L1s), in peripheral blood mononuclear cell (PBMC) DNA, a documented biomarker of CIN risk.

Methods

The study included 457 US women diagnosed with either CIN 2+ (cases) or ≤ CIN 1 (non-cases). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors for CIN.

Results

The 677CT/TT MTHFR genotypes were not associated with the risk of CIN 2+. Women with CT/TT genotype with lower folate, however, were more likely to be diagnosed with CIN 2+ compared to women with CT/TT genotype with higher folate (OR = 2.41, P = 0.030). Women with CT/TT genotype with lower folate were less likely to have a higher degree of PBMC L1 methylation compared to women with CT/TT genotype with higher folate (OR = 0.28, P = 0.017).

Conclusions

This study provides the first evidence that the MTHFR 677CT/TT genotype-associated lower degree of PBMC L1 methylation increases the risk of CIN 2+ in women in the US post-FA fortification era. Thus, even in the post-FA fortification era, not all women have adequate folate status to overcome MTHFR 677CT/TT genotype-associated lower degree of L1 methylation.  相似文献   

16.

Background

Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.

Methodology/Principal Findings

Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg''s funnel plot and Egger''s regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93–1.26; additive model: OR = 1.33, 95%CI = 0.81–2.17; dominant model: OR = 1.00, 95%CI = 0.86–1.15; recessive model: OR = 1.06, 95%CI = 0.77–1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88–1.41; additive model: OR = 1.36, 95%CI = 0.60–3.09; dominant model: OR = 1.25, 95%CI = 0.74–2.11; recessive model: OR = 2.17, 95%CI = 1.11–4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.

Conclusions/Significance

This meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.  相似文献   

17.

Background

Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual''s susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk.

Methods

A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08–2.12) or −634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03–1.50) was associated with the risk of PE, whereas there was no association between −2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82–1.16) or −1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94–1.78) polymorphism and PE risk in our study.

Conclusion

Our meta-analysis suggested that VEGF −2578C/A or −1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or −634G/C polymorphism and risk of PE.  相似文献   

18.

Objective

Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association.

Methods

All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).

Results

Ten studies with 6,774 cases and 9,772 controls were included for −1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for −765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to −765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113–1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295–3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297–3.970, P = 0.004). In subgroup analysis according to source of control, no significant association was detected. With respect to −1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses.

Conclusions

The present meta-analysis suggests that the COX-2 −765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer patients. Further large and well-designed studies are needed to confirm this association.  相似文献   

19.

Objective

To analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.

Methods

We carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association.

Results

7 studies were included. There was no significant association between IL-10 −1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001).

Conclusion

This meta-analysis indicates that IL10 −1082 A/G polymorphism is associated with IS susceptibility in Asians and the −1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.  相似文献   

20.

Background

Methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate and affects the activity of cellular cycles participating in nucleotide synthesis, DNA repair, genome stability, maintenance of methyl pool, and gene regulation. Genetically compromised MTHFR activity has been suggested to affect male fertility. The objective of the present study was to find the impact on infertility risk of c.203G>A, c.1298A>C, and c.1793G>A polymorphisms in the MTHFR gene.

Methods

PCR-RFLP and DNA sequencing were used to genotype the common SNPs in the MTHFR gene in 630 infertile and 250 fertile males. Chi-square test was applied for statistical comparison of genotype data. Linkage disequilibrium between the SNPs and the frequency of common haplotypes were assessed using Haploview software. Biochemical levels of total homocysteine (tHcy) and folic acid were measured. Meta-analysis on c.1298A>C polymorphism was performed using data from ten studies, comprising 2734 cases and 2737 controls.

Results

c.203G>A and c.1298A>C were found to be unrelated to infertility risk. c.1793G>A was protective against infertility (P = 0.0008). c.677C>T and c.1793G>A were in significant LD (D’ = 0.9). Folic acid and tHcy level did not correlate with male infertility. Pooled estimate on c.1298A>C data from all published studies including our data showed no association of this polymorphism with male infertility (Odds ratio = 1.035, P = 0.56), azoospermia (Odds ratio = 0.97, P = 0.74), or oligoasthenoteratozoospermia (Odds ratio = 0.92, p = 0.29). Eight haplotypes with more than 1% frequency were detected, of which CCGA was protective against infertility (p = 0.02), but the significance of the latter was not seen after applying Bonferroni correction.

Conclusion

Among MTHFR polymorphisms, c.203G>A and c.1298A>C do not affect infertility risk and c.1793G>A is protective against infertility. Haplotype analysis suggested that risk factors on the MTHFR locus do not extend too long on the DNA string.  相似文献   

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