Association of IL-6 − 174G > C and − 572C > G polymorphisms with risk of young ischemic stroke patients

Aim

To investigate the association between interleukin-6 (IL-6) − 174G > C and − 572C > G polymorphisms and risk for ischemic stroke (IS) in young patients.

Methods

We genotyped IL-6  − 174G > C and − 572C > G in a case–control study of 430 young IS patients and 461 control subjects. An unconditional multiple logistical regression model was used to calculate the effects of IL-6 − 174G > C and − 572C > G polymorphisms on IS risk.

Results

Higher body mass index, diabetes, hypertension, obesity, and smoking were associated with risk of ischemic stroke. Multivariate regression analyses showed that subjects carrying the − 174CC genotype (OR = 1.69, 95% CI = 1.16–2.57) and C allele (OR = 1.37, 95% CI = 1.09–1.67) had a small but significant increased risk of IS. Similarly, those carrying the − 572GG genotype (OR = 2.12, 95% CI = 1.18–3.82) and G allele (OR = 1.43, 95% CI = 1.14–1.83) had a moderate increased risk of IS. We found the − 174G > C and − 572C > G polymorphisms interact with hypertension and obesity.

Conclusion

Our results suggest that polymorphisms in IL-6 − 174G > C and − 572C > G are associated with IS risk in young patients, and that these polymorphisms interact with hypertension, obesity and etiologic subtypes. These findings could be helpful in identifying individuals at increased risk for developing IS.     

Associations of the PTEN − 9C>G polymorphism with insulin sensitivity and central obesity in Chinese

Background

Phosphatase and tensin homolog on chromosome 10 gene (PTEN) is known as a tumor-suppressor gene. Previous studies demonstrated that PTEN dysfunction affects the function of insulin. However, investigations of PTEN single nucleotide polymorphisms (SNPs) and IR-related disease associations are limited. The aim of the present study was to investigate whether its polymorphism could be involved in the risk of metabolic syndrome (MetS).

Methods

The genotype frequency of PTEN − 9C>G polymorphism was determined by using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) method in 530 subjects with MetS and 202 healthy control subjects of the Han Ethnic Chinese population in a case–control analysis.

Results

The PTEN − 9C>G polymorphism was not associated with MetS or its hyperglycemia, hypertension and hypertriglyceridemia components. In the control individuals aged < 60 years or ≥ 60 years, the CG genotype individuals had lower insulin sensitivity than CC individuals (P < 0.05). In the < 60-year-old MetS group and normal glucose tolerance (NGT) subgroup, the CG individuals had lower insulin sensitivity and higher waist circumference (WC) and waist-height-ratio (WHtR) than CC individuals (P < 0.05). Multiple linear regression analysis showed that the PTEN polymorphism (P = 0.001) contributed independently to 4.2% (adjusted R²) of insulin sensitivity variance (estimated by Matsuda ISI), while age (P = 0.004), gender (P = 0.000) and the PTEN polymorphism (P = 0.032) contributed independently to 5.6% (adjusted R²) of WHtR variance.

Conclusions

The CG genotype of PTEN − 9C>G polymorphism was not associated with MetS and some of its components as well. However, it may not only decrease insulin sensitivity in the healthy control and MetS in pre-elderly or NGT subjects, but may also increase the risk of central obesity among these MetS individuals.     

Synergistic effect of anti and pro-inflammatory cytokine genes and their promoter polymorphism with ST-elevation of myocardial infarction

Background

The single-gene approach in association studies of polygenic diseases such as acute myocardial infarction (AMI) is likely to provide limited value. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) plasma levels may be genetically influenced.

Aim

We evaluate the impact of single nucleotide polymorphism of the promoter region of these genes, as well as reciprocal interaction of these genes with ST-elevation of myocardial infarction (STEMI).

Methods

In a case–control study 500 STEMI patients and 500 age- and sex-matched controls were studied. Three single-nucleotide polymorphism genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis and assessed their association with STEMI. The synergistic effects of IL-6, TNF-α and IL-10 gene polymorphisms were evaluated by using logistic regression analysis.

Results

We found that IL-6 and TNF-α concentrations of studied population were significantly different (p < 0.0001) in each genotype of IL-6 − 174G>C and TNF-α − 308G>A gene polymorphisms respectively. A significant association was found in multivariate analysis for the IL-6 − 174G>C [odds ratio (OR): 0.390; 95% confidence interval (CI): 0.176–0.865, p = 0.020] and TNF-α − 308G>A [OR: 0.372; 95% CI: 0.171–808, p = 0.012] gene polymorphisms with STEMI. In contrast, IL-10 − 592C>A gene polymorphism was no longer significant in the multivariate model (OR: 0.678; 95% CI: 0.288 to 1.594, p = 0.373) whereas significant in univariate analysis (OR: 0.697; 95% CI: 0.523–0.929, p = 0.014).

Conclusions

Our findings suggest that IL-6, TNF-α and IL-10 gene polymorphisms all contribute in the association with STEMI whereas the association persisted only for IL-6 and TNF-α but not for IL-10 gene polymorphism with this disease in the multivariate analysis.     

CD53, a suppressor of inflammatory cytokine production,is associated with population asthma risk via the functional promoter polymorphism − 1560 C>T

Background

In this study, the association of asthma with CD53, a member of the tetraspanin family, was assessed for the first time in a mechanism-based study.

Methods

Genetic polymorphisms of CD53 were analyzed in 591 subjects and confirmed in a replication study of 1001 subjects. CD53 mRNA and protein levels were measured in peripheral blood leukocytes, and the effects of the promoter polymorphisms on nuclear factor binding were examined by electrophoretic mobility shift assay. Cellular functional studies were conducted by siRNA transfections.

Results

Among tagging SNPs of CD53, the − 1560 C>T in the promoter region was significantly associated with asthma risk. Compared with the CC genotype, the CT and TT genotypes were associated with a higher asthma risk, with odd ratios of 1.74 (P = 0.009) and 2.03 (P = 0.004), respectively. These findings were confirmed in the replication study with odd ratios of 1.355 (P = 0.047) and 1.495 (P = 0.039), respectively. The − 1560 C>T promoter SNP had functional effects on nuclear protein binding as well as mRNA and protein expression levels in peripheral blood leukocytes. When CD53 was knocked down by siRNA in THP-1 human monocytic cells stimulated with house dust mite, the production of inflammatory cytokines as well as NFκB activity was significantly over-activated, suggesting that CD53 suppresses over-activation of inflammatory responses.

Conclusions

The − 1560 C>T SNP is a functional promoter polymorphism that is significantly associated with population asthma risk, and is thought to act by directly modulating nuclear protein binding, thereby altering the expression of CD53, a suppressor of inflammatory cytokine production.     

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.     

Association between 1603C>T polymorphism of DBH gene and bipolar disorder in a Turkish population

Objectives

Dopamine-β-hydroxylase (DBH) is the enzyme responsible for the conversion of dopamine (DA) to norepinephrine (NE, noradrenaline) which is a key neurotransmitter in the central and peripheral nervous systems. Bipolar disorder is a major psychiatric disorder. The present study was designed to explore the associations of polymorphisms of DBH gene in Turkish patients with bipolar disorder.

Methods

− 1021C>T (rs1611115) polymorphism in promoter region, 444G>A (rs1108580) polymorphism in exon 2 and 1603C>T (rs6271; C535R) polymorphism in exon11 of DBH gene were analyzed in 106 patients with bipolar disorder and 106 healthy subjects by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.

Results

The results showed statistically significant associations for genotypic and allelic distribution between the 1603C>T polymorphism and bipolar disease (p = 0.0012 and p = 0.034, respectively). There was no association observed between the genotype and allelic frequencies for − 1021C>T and 444G>A polymorphisms and bipolar disorder.

Conclusions

Our data suggests that the 1603C>T polymorphism of the DBH gene is associated with susceptibility to bipolar disorder in a Turkish population.     

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.     

COX-2 polymorphisms − 765G→C and − 1195A→G and hepatocellular carcinoma risk

Cyclooxygenase-2 (COX-2) is overexpressed in hepatocellular carcinoma (HCC) and considered to play a role in hepatic carcinogenesis. Our aim was to examine the associations between polymorphisms in COX-2 − 765G→C and − 1195A→G and risk of HCC. We conducted a case–control study including 120 patients with HCC and 130 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms − 765G→C and − 1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. No significant difference was observed in the genotype distribution of the − 765G→C polymorphism between patients and controls. The − 1195AA genotype was associated with an increased risk of developing HCC (OR, 2.5; 95%CI, 1.18–5.37). The A allele was present significantly more often in HCC patients (OR 1.5; 95%CI, 1.05–2.14). In conclusion, our results demonstrated that the − 1195AA genotype and A allele have an important role in HCC risk in Egyptian patients.     

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.     

NQO1 609C > T polymorphism interaction with tobacco smoking and alcohol drinking increases colorectal cancer risk in a Chinese population

Background

NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case–control study to evaluate the potential association between NQO1 609C > T polymorphisms and colorectal cancer risk in a Chinese population.

Methods

The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations.

Results

The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR = 2.02, 95% CI = 1.55–2.57; TT: adjusted OR = 2.51, 95% CI = 1.82–3.47), compared with the CC genotype. Moreover, NQO1 609C > T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk.

Conclusion

Our findings suggest that the NQO1 609C > T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking.     

Influence of interleukin-6 gene − 174G>C polymorphism on development of atherosclerosis: A meta-analysis of 50 studies involving 33,514 subjects

Increasing epidemiological studies have focused on the associations between interleukin-6 (IL-6) gene − 174G>C polymorphism and atherosclerotic diseases, but the results are still controversial. This meta-analysis was designed to identify whether this association exists. PubMed, Embase, Web of Science, Cochrane database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the IL-6 gene − 174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses were made on the following: ethnicity, atherosclerotic diseases and source of controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in this meta-analysis. Overall, no significant association was found between the IL-6 gene − 174G>C polymorphism and AS risk (for C allele vs. G allele: OR = 1.02, 95% CI = 0.94–1.11, p = 0.64; for C/C vs. G/G: OR = 1.01, 95% CI = 0.85–1.21, p = 0.88; for C/C vs. C/G + G/G: OR = 0.97, 95% CI = 0.84–1.12, p = 0.68; for C/C + C/G vs. G/G: OR = 1.07, 95% CI = 0.97–1.17, p = 0.18). In the subgroup analyses, significant associations were found between the IL-6 gene − 174G>C polymorphism and AS in non-Caucasian group (for CC + CG vs. GG: OR = 1.22, 95% CI = 1.06–1.41, p = 0.005), other atherosclerotic diseases group (for C allele vs. G allele: OR = 0.75, 95% CI = 0.61–0.93, p = 0.008; for C/C vs. G/G: OR = 0.56, 95% CI = 0.38–0.81, p = 0.002; for C/C vs. C/G + G/G: OR = 0.60, 95% CI = 0.45–0.79, p = 0.0004) and population-based group (for C allele vs. G allele: OR = 1.09, 95% CI = 1.00–1.18, p = 0.04; for CC + CG vs. GG: OR = 1.15, 95% CI = 1.04–1.27, p = 0.005). In summary, the present meta-analysis suggests that the IL-6 gene − 174G C polymorphism is associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution.     

CHK2 1100delC,IVS2 + 1G>A and I157T mutations are not present in hepatocellular cancer cases from a Turkish population

Aim

The cell cycle checkpoint kinase 2 (CHK2) protein participates in the DNA damage response in many cell types. Germline mutations in CHK2 (1100delC, IVS2 + 1G>A and I157T) have been associated with a range of cancer types. This study aimed to investigate whether CHK2 1100delC, IVS2 + 1G>A and I157T mutations play an important role in the development of hepatocellular carcinoma (HCC) in a Turkish population.

Methods

A total of 165 hepatocellular cancer cases and 446 cancer-free controls were genotyped for CHK2 mutations by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-polymerase chain reaction (AS-PCR) methods.

Results

We did not find CHK2 1100delC, IVS2 + 1G>A and I157T mutations in any of 611 Turkish subjects.

Conclusion

Our results demonstrate for the first time that CHK2 1100delC, IVS2 + 1G>A and I157T mutations have not been a genetic susceptibility factor for HCC in the Turkish population. Overall, our data suggests that genotyping of CHK2 mutations in clinical settings in the Turkish population should not be recommended. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.     

Update meta-analysis on MMP-7 − 181A>G polymorphism and cancer risk: Evidence from 25 studies

Background

The matrix metalloproteinase (MMP) can degrade various components of the extracellular matrix and its functional genetic polymorphism may be associated with cancer development. The common MMP-7 (− 181A>G) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between MMP-7 (− 181A>G) and cancer risk remains inconclusive.

Methods

To better understand the role of MMP-7 (− 181A>G) polymorphism in global cancer, we conducted this comprehensive meta-analysis encompassing 6392 cases and 7665 controls.

Results

Overall, the MMP-7 (− 181A>G) polymorphism was associated with higher cancer risk. In the stratified analyses, significant associations were found between the MMP-7 (− 181A>G) polymorphism and gastric cancer, ESCC and gynecologic cancer. We also observed that the GG genotype might modulate colorectal cancer risk comparing with the AA genotype (OR = 1.31[1.02–1.69]). Moreover, a significantly increased cancer risk was found among Asian populations. When stratified by study design, significantly elevated susceptibility to cancer was found among population-based studies.

Conclusions

These findings suggested that the MMP-7 (− 181A>G) genetic polymorphism may contribute to the susceptibility of cancers, especially among Asian population.     

The impact of GGH -401C > T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancer

Aims

Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C > T polymorphism in treatment response in cervical cancer.

Methods

We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C > T SNP were determined by real-time PCR and statistical analysis was performed by χ² test and survival analysis.

Results

The genotypes of GGH-401C > T were significantly associated with the response to platinum-based chemoradiotherapy. Treatment response was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p = 0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR = 3.036; CI 95% 1.032-8.934, p = 0.044).

Conclusions

The results of our study suggested the potential interest of GGH -401C > T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.     

Uncoupling protein 2 − 866G/A and uncoupling protein 3 − 55C/T polymorphisms in young South African Indian coronary artery disease patients

Background

Uncoupling proteins (UCPs) 2 and 3 play an important role in the regulation of oxidative stress which contributes to chronic inflammation. Promoter polymorphisms of these genes have been linked to chronic diseases including heart disease and type II diabetes mellitus in several populations. This is the first investigation of the UCP2 − 866G/A rs659366 and UCP3 − 55C/T rs1800849 polymorphisms in young South African (SA) Indians with coronary artery disease (CAD).

Methods

A total of 300 subjects were recruited into this study of which 100 were SA Indian males with CAD, 100 age- (range 24–45 years), gender- and race-matched controls and 100 age-matched black SA males. The frequency of the UCP2 − 866G/A and UPC3 − 55C/T genotypes was assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

Results

The heterozygous UCP2 − 866G/A and homozygous UCP3 − 55C/C genotypes occurred at highest frequency in CAD patients (60% and 64%, respectively) compared to SA Indian controls (52% and 63%) and SA Black controls (50% and 58%). The UCP2 − 886G/A (OR = 1.110; 95% CI = 0.7438–1.655; p = 0.6835) and UCP3 − 55C/T (OR = 0.788; 95% CI = 0.482–1.289; p = 0.382) polymorphisms did not influence the risk of CAD.The rare homozygous UCP3 − 55T/T genotype was associated with highest fasting glucose (11.87 ± 3.7 mmol/L vs. C/C:6.11 ± 0.27 mmol/L and C/T:6.48 ± 0.57 mmol/L, p = 0.0025), HbA1c (10.05 ± 2.57% vs. C/C:6.44 ± 0.21% and C/T:6.76 ± 0.35%, p = 0.0006) and triglycerides (6.47 ± 1.7 mmol/L vs. C/C:2.33 ± 0.17 mmol/L and C/T:2.06 ± 0.25 mmol/L, p < 0.0001) in CAD patients.

Conclusion

The frequency of the UCP2 − 866G/A and UCP3 − 55C/T polymorphisms was similar in our SA Indian and SA Black groups. The presence of the UCP2 − 866G/A and UCP3 − 55C/T polymorphisms does not influence the risk of CAD in young South African Indian CAD patients.     

Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

Background

Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection.

Methods

Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI).

Results

A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup.

Conclusion

Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results.     

Association of functional FEN1 genetic variants and haplotypes and breast cancer risk

Aim

As a tumor suppressor, FEN1 plays an essential role in preventing tumorigenesis. Two functional germline variants (-69G > A and 4150G > T) in the FEN1 gene have been associated with DNA damage levels in coke-oven workers and multiple cancer risk in general populations. However, it is still unknown how these genetic variants are involved in breast cancer susceptibility.

Methods

We investigated the association between these polymorphisms and breast cancer risk in two independent case–control sets consisted of a total of 1100 breast cancer cases and 1400 controls. The influence of these variations on FEN1 expression was also examined using breast normal tissues.

Results

It was found that the FEN1-69GG genotypes were significantly correlated to increased risk for developing breast cancer compared with the -69AA genotype in both sets [Jinan set: odds ratios (OR) = 1.41, 95% confidence interval (CI) = 1.20–1.65, P = 1.9×10^− 5; Huaian set: OR = 1.51, 95% CI = 1.22–1.86, P = 1.7×10^− 4]. Similar results were observed for 4150G > T polymorphism. The genotype–phenotype correlation analyses demonstrated that the -69G or 4150G allele carriers had more than 2-fold decreased FEN1 expression in breast tissues compared with -69A or 4150T carriers, suggesting that lower FEN1 expression may lead to higher risk for malignant transformation of breast cells.

Conclusion

Our findings highlight FEN1 as an important gene in human breast carcinogenesis and genetic variants in FEN1 confer susceptibility to breast cancer.     

The interleukin-4 − 589C/T polymorphism and the risk of asthma: A meta-analysis including 7345 cases and 7819 controls

Background

A number of studies assessed the association of − 589C/T polymorphism in the promoter region of interleukin-4 (IL-4) with asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to investigate the association between polymorphism in the IL-4 and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Thirty-four studies involving 7345 cases and 7819 controls were included. Overall, significant association between − 589C/T polymorphism and asthma was observed for TT + CT vs. CC (OR = 1.26; 95% CI 1.12–1.42; P = 0.0001; I² = 26%). In the subgroup analysis by ethnicity, significant associations were found among Asians (OR = 1.36; 95% CI 1.07–1.73; P = 0.01; I² = 0%) and Caucasians (OR = 1.30; 95% CI 1.09–1.54; P = 0.004; I² = 53%) but not among African Americans (OR = 1.20; 95% CI 0.72–2.00; P = 0.48; I² = 48%). In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR = 1.20; 95% CI 0.92–1.34; P = 0.27; I² = 6%) and non-atopic asthma patients (OR = 0.97; 95% CI 0.73–1.28; P = 0.81; I² = 0%).

Conclusions

This meta-analysis suggested that the IL-4 − 589C/T polymorphism was a risk factor of asthma.     

Polymorphisms of folate metabolism-related genes and survival of patients with colorectal cancer in the Korean population

Background

5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival.

Patients and methods

We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C > T and 1298A > C, and RFC1 − 43T > C, 80G > A, and 696C > T. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS).

Results

The combined TS 1494 0bp6bp + 6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 − 43CC and 80AA genotypes were associated with favorable OS.

Conclusions

Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings.