Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.     

Association between -251A>T polymorphism in the interleukin-8 gene and oral cancer risk: A meta-analysis

Background

Emerging evidence showed that the most common functional polymorphism (-251A>T, rs4073) in the promoter region of the interleukin-8 (IL-8) gene is involved in the regulation of the activities of interleukin-8, thus increasing an individual's susceptibility to oral cancer; but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between IL-8 -251A>T polymorphism and oral cancer risk.

Methods

The PubMed, Embase, Web of Science and CBM databases were searched for all articles published up to October 1st, 2012 that addressed IL-8 -251A>T polymorphism and oral cancer risk. Statistical analyses were performed using STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Six case–control studies were included with a total of 1324 oral cancer cases and 1879 healthy controls. When all available studies were pooled into the meta-analysis, the results showed that the AA and AT genotypes of IL-8 -251A>T polymorphism were associated with increased risk of oral cancer (OR = 1.23, 95% CI: 1.03–1.46, P = 0.025; OR = 1.25, 95% CI: 1.07–1.47, P = 0.006; respectively). In the subgroup analysis by ethnicity, significant associations were observed between the AA and AT genotypes of IL-8 -251A>T polymorphism and increased risk of oral cancer among Caucasian populations (OR = 1.40, 95% CI: 1.14–1.72, P = 0.001; OR = 1.29, 95% CI: 1.06–1.57, P = 0.011; respectively). However, no statistically significant associations were found between IL-8 -251A>T polymorphism and oral cancer risk among Asian populations.

Conclusions

Results from the current meta-analysis indicate that the AA and AT genotypes of IL-8 -251A>T polymorphism might increase the risk of oral cancer, especially among Caucasian populations.     

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis

Aims

Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.

Results

Ten published case–control studies including a total of 1494 cases and 2259 controls were identified. Overall, significant risk effects of Lys751Gln genotype was found under the dominant model (OR = 1.16; 95% CI = 1.01–1.34; P = 0.032). When stratified by clinical types, the variant genotype was associated with the acute myeloid leukemia (AML) risk under the heterozygote comparison (OR = 1.20; 95% CI = 1.00–1.43; P = 0.048), the homozygote comparison (OR = 1.35; 95% CI = 1.05–1.74; P = 0.019) and the dominant model (OR = 1.23; 95% CI = 1.04–1.45; P = 0.015), respectively. Furthermore, significantly increased risks were also pronounced in Caucasian AML patients (the homozygote comparison: OR = 1.38; 95% CI = 1.07–1.78; P = 0.013; the dominant model: OR = 1.23; 95% CI = 1.03–1.46; P = 0.020; and the recessive model: OR = 1.26; 95% CI = 1.00–1.60; P = 0.050). No evident heterogeneities were observed for the overall data under all genetic models. In addition, no statistical evidence for publication bias was found using the method of Begg's and Egger's tests.

Conclusion

This meta-analysis suggested that XPD Lys751Gln polymorphism might be a risk factor for AML and Caucasian acute leukemia patients.     

Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children

Background and aims

Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children.

Methods

A total of 1037 non-related Mexican children aged 6 to 12 years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants.

Results

Elevated ALT levels (> 35 U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR = 3.7, 95% CI 2.3–5.9; P = 3.7 × 10^− 8), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P = 0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR = 19.9, 95% CI 2.5–157.7; P = 0.005) than overweight and obese children (OR = 3.4, 95% CI 1.3–8.9; P = 0.014 and OR = 3.1, 95% CI 1.7–5.5; P = 1.4 x10^− 4, respectively).

Conclusions

The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population.     

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo

Background

Some studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo.

Aims

The purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo.

Methods

We carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0.

Results

Six case–control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR = 1.59, 95% CI: 1.21–2.08, P = 0.001; GSTT1: OR = 1.30, 95% CI: 1.12–1.51, P = 0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR = 1.71, 95% CI: 1.12–2.63, P = 0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR = 1.76, 95% CI: 1.15–2.71, P = 0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans.

Conclusion

The GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.     

Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease

Purpose

A number of studies reported on associations of single nucleotide polymorphisms (SNPs) present in chromosome 9p21 with early-onset coronary artery disease (CAD). The present study was then undertaken to perform a meta-analysis of all the results published to date.

Methods

All studies of the 9p21 association with early-onset CAD that were published between 2007 and 2012 were retrieved from the PubMed database. RevMan 5.0 software was used to perform meta-analysis of the data that fulfilled the criteria for our meta-analysis. The effect size of four SNPs in the 9p21 region on early-onset CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI).

Results

A total of 7123 subjects from 7 case–control studies were genotyped. Meta-analysis demonstrated disease association for rs2383207 (OR = 0.79, 95% CI 0.71–0.88, P < 0.0001), rs2383206 (OR = 1.17, 95% CI 1.10–1.25, P < 0.00001), rs10757278 (OR = 1.28, 95% CI 1.15–1.42, P < 0.00001), and rs10757274 (OR = 1.17, 95% CI 1.08–1.33, P = 0.02).

Conclusion

Genetic variation in the chromosome 9p21 region may contribute to the etiology of early-onset CAD although their effect size is rather small.     

Polymorphisms of the TLR4 gene and risk of gastric cancer

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.     

Secretoglobin 1A member 1 (SCGB1A1) + 38A/G polymorphism is associated with asthma risk: A meta-analysis

Background

Epidemiological studies have evaluated the association between Secretoglobin 1A member 1 (SCGB1A1) + 38A/G polymorphism and asthma, but the results remain inconclusive. The aim of this study was to perform a meta-analysis to investigate a more authentic association between SCGB1A1 + 38A/G polymorphism and asthma.

Methods

Published literature from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed-effect model according the between-study heterogeneity.

Results

A total of 19 case-control studies in 18 articles were included in the meta-analysis, including 3191 cases and 5182 controls. We found that SCGB1A1 + 38A/G polymorphism was associated with a significantly increased risk of asthma risk when all studies were pooled in a dominant model (OR = 1.29; 95% CI 1.08–1.54; P = 0.005). The cumulative meta-analysis and sensitivity analysis further strengthened the stability of the result. Furthermore, publication bias was not detected.

Conclusions

This study suggested that SCGB1A1 + 38A/G polymorphism was a risk factor for asthma. Further large and well-designed studies are needed to confirm this association.     

Role of CYP1A2*1F polymorphism in cancer risk: Evidence from a meta-analysis of 46 case–control studies

Background

Emerging evidence showed that the common polymorphism (CYP1A2*1F, rs762551 C → A) in the promoter region of the CYP1A2 gene might be associated with susceptibility to cancer in humans. But individually published results were inconclusive. The aim of this meta-analysis is to investigate the association between CYP1A2*1F polymorphism and cancer risk.

Methods

The Pubmed, Embase, Web of Science and Chinese BioMedical databases were searched for all articles published up to September 1st, 2012. Statistical analyses were performed using the STATA 12.0 software.

Results

Forty-six case–control studies were included with a total of 22,993 cancer cases and 28,420 healthy controls. Meta-analysis results showed that the A allele of CYP1A2*1F polymorphism was associated with a decreased cancer risk (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.87–0.98, P = 0.013). In the subgroup analysis by cancer types, the A allele of CYP1A2*1F polymorphism may increase the risk of breast cancer (OR = 1.05, 95% CI: 1.01–1.10, P = 0.024), and is also associated with a decreased risk of ovarian cancer (OR = 0.70, 95% CI: 0.54–0.89, P = 0.004). However, similar results were not found in lung, colorectal, bladder, endometrial, pancreatic and gastric cancers. Further subgroup analysis by ethnicity also showed a significant association between the A allele of CYP1A2*1F polymorphism and a decreased cancer risk among Caucasian populations (OR = 0.91, 95% CI: 0.84–0.98, P = 0.014); but no significant associations were observed among Asian populations.

Conclusions

Results from the current meta-analysis indicate that the A allele of CYP1A2*1F polymorphism may be associated with breast and ovarian cancer risk, especially among Caucasian populations.     

Combined effect between CHRNB3–CHRNA6 region gene variant (rs6474412) and smoking in psoriasis vulgaris severity

Background

Many factors associated with causing psoriasis have been reported, such as the genetic and environmental factors. Smoking is one of the well-established environmental risk factors for psoriasis and also associated with the disease severity. In addition, several studies of psoriasis and psoriatic arthritis have documented gene–environment interactions involving smoking behavior. Although gene polymorphisms on nicotinic acetylcholine receptor subunits CHRNB3–CHRNA6 region gene have been found to correlate with smoking behavior and lung cancer susceptibility in Chinese Han population, the combined effect between the smoking-related genetic variants and smoking behavior on psoriasis vulgaris (PV) has been unreported.

Objective

To evaluate the combined effect of the smoking-related (rs6474412-C/T) polymorphism on CHRNB3–CHRNA6 region gene and smoking behavior on PV risk and clinic traits in Chinese Han population.

Methods

A hospital-based case–control study including 672 subjects (355 PV cases and 317 controls) was conducted. The variant of rs6474412 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA).

Results

The higher body mass index (BMI ≥ 25), smoking behavior and alcohol consumption were risk factors for PV, and the estimated ORs were 1.55 (95% CI, 1.09–2.29), 1.74 (95% CI, 1.22–2.49) and 1.81 (95% CI, 1.25–2.62) respectively. The smoking patients had more severe conditions than non-smokers (OR = 1.71, 95% CI, 1.08–2.70, P = 0.020). The alleles and genotypes of rs6474412 were not associated with risk of PV, but the combined effect of rs6474412 genotype (TT) and smoking behavior increased severity of PV (OR = 5.95; 95% CI, 1.39–25.31; P < 0.05; adjusted OR = 2.20; 95% CI, 1.55–3.14; P < 0.001).

Conclusions

Our results demonstrate that the combined effect of rs6474412-C/T polymorphism in smoking-related CHRNB3–CHRNA6 region gene and smoking behavior may not confer risk to PV, but may have impact on PV severity in Chinese Han population.     

Association between IL13 gene polymorphisms and susceptibility to cancer: A meta-analysis

Background/aims

Interleukin-13 (IL13) is an immunoregulatory cytokine which plays an important role in carcinogenesis through affecting tumor immunosurveillance. Many studies had reported the influence of IL13 rs1800925 and rs20541 polymorphisms on cancer risk, however, with inconclusive results. The aim of the present study was to conduct a meta-analysis to clarify the relationship.

Methods

Twenty studies including a total of 6713 cancer cases and 8693 controls for IL13 rs20541 polymorphism and 4081 cancer cases and 6202 controls for IL13 rs1800925 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association.

Results

Overall, the IL13 rs20541 polymorphism were associated with significantly decreased cancer risk in all genetic models (AA vs. GG: OR = 0.82, 95%CI = 0.71–0.95; GA vs. GG: OR = 0.92, 95%CI = 0.85–0.99; GA/AA vs. GG: OR = 0.90, 95%CI = 0.85–0.97; AA vs. GG/GA: OR = 0.85, 95CI% = 0.74–0.98). In the stratified analyses, significant effects were found among European populations, studies with population-based controls and studies of glioma. No influence of the IL13 rs1800925 polymorphism on the overall cancer risk was observed. However, in the stratified analyses, we found the IL13 rs1800925 polymorphism was significantly associated with decreased risk for glioma (CT vs. TT: OR = 0.72, 95%CI = 0.55–0.93; CT/TT vs. TT: OR = 0.76, 95%CI = 0.62–0.89).

Conclusion

Our meta-analysis suggests that the IL13 rs20541 polymorphism contributes to susceptibility to cancer, especially for glioma; and the IL13 rs1800925 polymorphism may be associated with glioma risk.     

Association between ADAM33 S2 and ST+4 polymorphisms and susceptibility to asthma: A meta-analysis

Objective

The aim of this study was to determine whether ADAM33 (a disintegrin and metalloproteinase domain 33) polymorphisms confer susceptibility to asthma in different populations.

Methods

We performed a meta-analysis on the association between the ADAM33 S2, ST+4, F+1, S1, and V4 polymorphisms and asthma.

Results

Thirteen studies in ten reports, which included 4942 patients and 7933 controls, were available for the meta-analysis. Meta-analysis stratified by ethnicity indicated an association between the ADAM33 S2 2 allele and asthma in Europeans (OR = 0.912, 95% CI = 0.851–0.977, p = 0.009). Meta-analysis revealed an association between asthma and the ADAM33 ST+4 2 allele (OR = 0.783, 95% CI = 0.762–0.999, p = 0.048). Stratification by ethnicity indicated an association between the ADAM33 ST+4 polymorphism and asthma in Asians. Stratification by age indicated an association between the ADAM33 ST+4 2 allele and asthma in adults (OR = 0.863, 95% CI = 0.782–0.964, p = 0.008). However, no association was found between asthma and the ADAM33 F+1, S1, and V4 polymorphisms.

Conclusions

This meta-analysis demonstrates that the ADAM33 S2 polymorphism confers susceptibility to asthma in Europeans and the ADAM33 ST+4 polymorphism is associated with asthma in Asians and adults.     

The polymorphism − 1131T > C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects

Background

Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 − 1131T > C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia.

Methods

We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student–Newman–Keuls test.

Results

The minor allele C was more frequent in dyslipidemic subjects than controls (p = 0.019) and confers an increased individual risk for dyslipidemia (OR = 1.726, CI 95% = 1.095–2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p = 0.037; OR = 2.050, CI 95% = 1.042–4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p = 0.046 and 0.049, respectively).

Conclusions

The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 − 1131T > C polymorphism is associated with dyslipidemia in male subjects.     

Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

A genetic variant in the promoter of APE1 gene (− 656 T > G) is associated with breast cancer risk and progression in a Chinese population

Background/aims

APE1 is an important DNA repair protein in the base excision repair pathway. Genetic variations in APE1 have been suggested to influence individuals' susceptibility to human malignancies. The present study was aimed to investigate the associations between two functional polymorphisms in APE1 (− 656 T > G and 1349 T>G) and breast cancer risk.

Methods

We genotyped the two polymorphisms in a case-control study of 500 breast cancer patients and 799 age-matched cancer-free controls using the TaqMan method. Unconditional logistic regression adjusted for potential confounding factors was used to assess the associations.

Results

We found that the variant genotypes of the − 656 T>G were significantly associated with decreased breast cancer risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.56–0.91], and the protective effect of this polymorphism was more predominant among the subgroups of younger subjects (< 52 years) (OR = 0.65, 95% CI = 0.46–0.92). Besides, we found that the variant genotypes were associated with less frequent lymph node metastasis (P = 0.020, OR = 0.64, 95% CI = 0.44–0.94). We did not observe any significant association between the 1349 T>G polymorphism and breast cancer risk.

Conclusion

Our results suggest that the APE1 − 656 T>G but not the 1349 T>G polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population. Large population-based prospective studies are required to validate these findings.     

Association between the − 786T>C 1polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease: A systematic review and meta-analysis

Background

A variety of studies have evaluated the association between the − 786T>C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) and risk of coronary artery disease (CAD). However, the results remain conflicting. To better understand the role of eNOS − 786T>C polymorphism in CAD risk, we conducted a comprehensive systematic review and meta-analysis.

Methods

Case–control, cohort or cross-sectional studies evaluating the association between eNOS − 786T>C polymorphism and CAD risk were searched in electronic databases of PubMed, ISI Web of Knowledge, Medline, Embase and Google Scholar Search (up to January 2013). Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between eNOS − 786T>C polymorphism and CAD risk. Statistical analysis was performed with Review Manager 5.0 and STATA12.0.

Results

Twenty-four studies were analyzed between 6192 CAD cases and 9281 healthy controls. The combined results of overall analysis showed significant positive associations between CAD risk and eNOS − 786T>C polymorphism in dominant model (OR = 1.45, 95% CI = 1.27–1.65), recessive model (OR = 1.37, 95% CI = 1.20–1.56), homozygote comparison (OR = 1.64, 95% CI = 1.31–2.04), heterozygote comparison (TC vs. TT, OR = 1.39, 95% CI = 1.23–1.57; CC vs. TC, OR = 1.20, 95% CI = 1.04–1.37) and allele comparison (OR = 1.35, 95% CI = 1.21–1.50). On subgroup analysis based on the ethnicity of population (Caucasians, Asians and others), significant differences were found in all genetic models for Caucasians, similar associations existed in Asians except heterozygote comparison (CC vs. TC). However, the associations were only found in dominant model, heterozygote comparison (TC vs. TT) and allele comparison for the populations named others.

Conclusions

Our investigations demonstrate the significant associations between eNOS − 786C>T polymorphism and CAD risk, and this polymorphism might become an early marker for the risk evaluation of CAD.     

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: A meta-analysis

Aims

Data on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic.

Methods

We searched for case–control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated.

Results

Six case–control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72 + genotypes in Caucasians (OR = 0.79, 95% CI: 0.64–0.98, P_z = 0.030).

Conclusion

The ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion.     

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: A community-based case–control study

Objectives

There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease.

Methods

A community-based, case–control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.

Results

We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.35–0.81], rs2547547 [OR = 1.72, 95% CI: 1.13–2.64], and rs2530223 [OR = 1.39; 95% CI: 1.01–1.91]. Subgroup analysis showed that BMI ≥ 23 kg/m², high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27–0.91), 0.38 (95% CI: 0.20–0.71) and 0.43 (95% CI: 0.24–0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25–0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17–3.15) and 2.24 (95% CI: 1.28–3.94) when compared with the population carrying the AA genotype.

Conclusions

The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.     

Population-based and family-based studies on the protein tyrosine phosphatase non-receptor 22 gene polymorphism and type 1 diabetes: A meta-analysis

Purpose

Studies investigating the association between PTPN22 gene C1858T polymorphism and type 1 diabetes (T1D) susceptibility among Caucasian population have reported conflicting results. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the PTPN22 C1858T polymorphism and T1D.

Methods

Databases including PubMed, Web of Science, and EMBASE were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.

Results

In total, 33 population-based studies with 22, 485 cases and 35, 292 controls, 9 family-based studies involving 7276 families were included. Under the random-effects model, the per-allele overall OR of the C1858T polymorphism for T1D was 1.89 (95% CI: 1.76–2.02, P < 10^− 5) by pooling all available case–control studies. In addition, we found significant evidence for overtransmission of the risk T allele in family-based studies (overall OR _TDT = 1.58, 95% CI: 1.43–1.74; P < 10^− 5). The summary OR from case–control and family-based association studies was 1.81 (95% CI: 1.70–1.93, P < 10^− 5).

Conclusions

In conclusion, this meta-analysis suggests that C1858T polymorphism in PTPN22 is associated with elevated T1D risk among Caucasian population.