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.     

Are glutathione S-transferase polymorphisms (GSTM1, GSTT1) associated with primary open angle glaucoma? A meta-analysis

Background

Glutathione S-transferase (GST) variants have been considered as risk factors for the pathogenesis of primary open angle glaucoma (POAG). However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for POAG.

Methods

Published literature from PubMed and EMBASE databases was retrieved. All studies evaluating the association between GSTM1/GSTT1 variants and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model.

Results

14 studies (1711 POAG cases and 1537 controls) were included in the meta-analysis of GSTM1 genotypes and 10 studies (1306 POAG cases and 1114 controls) were included in the meta-analysis of GSTT1 genotypes. The overall result showed that the association between GSTM1 and GSTT1 null genotypes and risk for POAG was not statistically significant (GSTM1: OR = 1.19, 95% CI = 0.82–1.73, p = 0.361; GSTT1: OR = 1.26, 95% CI = 0.77–2.06, p = 0.365). The results by ethnicity showed that the association between the GSTM1 null genotype and risk for POAG is statistically significant in East Asians (OR = 1.41, 95% CI = 1.04–1.90, p = 0.026), but not in Caucasians (OR = 1.13, 95% CI = 0.69–1.84, p = 0.638) and Latin-American (OR = 1.09, 95% CI = 0.62–1.92, p = 0.767). In addition, there was no significant association of GSTT1 null genotype with risk for POAG in either ethnic population.

Conclusions

The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with POAG risk in East Asians.     

Association of peroxisome proliferator activated receptor-γ gene with non-alcoholic fatty liver disease in Asian Indians residing in north India

Background

Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD.

Methods

In this case–control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction–restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed.

Results

Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist–hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p = 0.04), total cholesterol (p = 0.01), ALK (p = 0.04) and gamma-glutamyl transpeptidase (p = 0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1 = 0.1; p = 0.006) and controls (D1 = 0.07; p = 0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09–2.45, p = 0.05)].

Conclusion

Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD.     

Association between interleukin-6 gene − 174 G/C polymorphism and the risk of coronary heart disease: A meta-analysis of 20 studies including 9619 cases and 10,919 controls

Interleukin-6 (IL-6) gene − 174 G/C polymorphism has been reported to be associated with coronary heart disease (CHD), but the results remain inconclusive. The present meta-analysis was therefore designed to clarify these controversies. This meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 20 studies including 9619 CHD cases and 10,919 controls were combined showing no evidence of association between IL-6 gene − 174 G/C polymorphism and CHD risk (for C/C + C/G vs. G/G: OR = 1.10, 95% CI = 0.99–1.22, p = 0.07; for C/C vs. C/G + G/G: OR = 1.08, 95% CI = 0.93–1.24, p = 0.33; for C/C vs. G/G: OR = 1.16, 95% CI = 0.97–1.39, p = 0.11; for C allele vs. G allele: OR = 1.10, 95% CI = 1.00–1.21, p = 0.06). Moreover, we also did not find significant association between IL-6 gene − 174 G/C polymorphism and myocardial infarction (MI) risk. However, in the subgroup analysis by ethnicity, significant association was found among Asians (for C/C + C/G vs. G/G: OR = 1.35, 95% CI = 1.05–1.63, p = 0.02). In summary, the present meta-analysis suggests that IL-6 gene − 174 G/C polymorphism is associated with increased CHD risk among Asians. However, due to the small subjects included in the subgroup analysis of Asians, the results should be interpreted with caution.     

Impact of MMP-3 and TIMP-3 gene polymorphisms on prostate cancer susceptibility in North Indian cohort

Purpose

Matrix metalloproteinases (MMPs) have been implicated in progression and metastases of different tumors. The balance between the MMPs and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seem to be an important factor related to its role. The purpose of this study was to evaluate polymorphisms in the MMP-3 and TIMP-3 genes for their associations with prostate cancer (PCa) risk in North Indians.

Materials and methods

Genotypes were determined by PCR-RFLP (Polymerase Chain Reaction Restriction Fragment Length Polymorphism) method in 150 PCa patients and 200 age matched controls of similar ethnicity.

Results

We found significant association in the MMP-3(1171)5A/6A and TIMP-3 (1298) C/T polymorphism with PCa risk. Variant genotype (5A/5A) of MMP-3(1171)5A/6A polymorphism had a high PCa risk (p = 0.037, OR = 3.52, 95%CI = 1.08–11.5). Individuals with TIMP-3 (1298) CT genotype as well as T allele showed reduced risk of PCa (p < 0.001; OR = 0.31; 95%CI = 0.18–0.52, and p = 0.001; OR = 0.49; 95%CI = 0.32–0.75). This effect was even more evident in case of T allele carrier (CT + TT) (p < 0.001; OR = 0.36; 95%CI = 0.22–0.59). Overall no significant association was observed statistically in MMP-3 and TIMP-3 with any of the grading stages and smoking habits in PCa. Haplotype analysis of MMP-3 showed that A-5A-A was associated with three folds (OR = 3.06; 95%CI = 1.71–5.47; p < 0.001) increased risk in PCa patients.

Conclusion

This is the first reported association between polymorphisms in the MMP-3 and TIMP-3 gene and PCa risk and supports the hypothesis that the protease/antiprotease balance has an important role. Due to the small sample size further investigations need to be done to prove a statistical significant correlation between the MMP/TIMP expression and clinicopathological parameters.     

Association study of CD36 single nucleotide polymorphisms with essential hypertension in the Northeastern Han Chinese

We found that cluster determinant 36 (CD36) gene is up-regulated in essential hypertension (EH) patients in our former research, but the association between CD36 gene variations and EH has not yet been clearly demonstrated. The relationship between CD36 gene single nucleotide polymorphisms (SNPs) and EH in the northeastern Han Chinese was examined in the present study through direct sequencing and genotype-detection. A total of 589 unrelated northeastern Han Chinese including 276 with EH and 313 controls were studied. SNPs in exon 7, exon 13 and intron 4 were detected using PCR-sequencing. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). + 216T/C, + 273A/G, + 132C/T, + 217T/C, + 212T/G and + 233T/C polymorphisms were identified. Distributions of genotypes AA, GA and GG of + 273A/G polymorphism were significantly different between EH group and the control group (χ²: 9.056, p = 0.011) and G allelic frequency was higher in EH (p = 0.006, OR = 1.629, 95% CI [1.224–2.168]). Logistic regression analysis showed that + 273A/G polymorphism was closely associated with blood pressure (BP) after adjusting for ages. When subclassified by sex, the genotype distribution of + 273A/G (p = 0.011) and allelic frequency of G allele (p = 0.006) were significantly different between EH participants and controls in males, but not in females. Subgroup analysis performed by body mass index (BMI) suggested that the genotype distribution of + 273A/G and allelic frequency were significantly different in non-obese group and non-obese men, but the associations were not significant (non-obese group: p = 0.016, OR = 1.664, 95% CI [1.459–2.409]; non-obese men: p = 0.073, OR = 1.898, 95% CI [1.033–3.487]). + 273A/G polymorphism in CD36 gene was associated with EH, and + 273G could be an independent predictor.     

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 of the macrophage migration inhibitory factor gene − 173G/C polymorphism with inflammatory bowel disease: A meta-analysis of 4296 subjects

A variety of epidemiologic studies have focused on the association between macrophage migration inhibitory factor (MIF) gene − 173G/C polymorphism and inflammatory bowel disease (IBD). However, results in different studies have been inconsistent. In order to derive a more precise estimation of the associations, we performed this meta-analysis and systematic searches of electronic databases PubMed and Web of Science (up to April 30, 2013). Based on our search criteria, a total of seven eligible studies concerning the MIF − 173G/C polymorphism and IBD risk were included in the final meta-analysis, comprising 2162 IBD cases and 2134 controls. Significant association was found between MIF − 173G/C polymorphism and the risk of IBD when all studies were pooled into the meta-analysis (for C allele vs. G allele: OR = 1.25, 95% CI = 1.12–1.41, p = 0.000; for C/C vs. G/G: OR = 1.71, 95% CI = 1.23–2.39, p = 0.002; for C/C + G/C vs. G/G: OR = 1.24, 95% CI = 1.09–1.42, p = 0.002; for C/C vs. G/C + G/G: OR = 1.67, 95% CI = 1.20–2.33, p = 0.002). Heterogeneity and publication bias did not exist in the overall comparisons. The present meta-analysis suggests an association between the MIF − 173G/C polymorphism and IBD risk. However, due to few studies and the selection bias existed in some studies, the results should be interpreted with caution.     

Promoter polymorphisms in trefoil factor 2 and trefoil factor 3 genes and susceptibility to gastric cancer and atrophic gastritis among Chinese population

The polymorphisms in trefoil factor (TFF) gene family that protect gastrointestinal epithelium might influence individual vulnerability to gastric cancer (GC) and atrophic gastritis. We used the Sequenom MassARRAY platform to identify the genotypes of TFF2 rs3814896 and TFF3 rs9981660 polymorphisms in 478 GC patients, 652 atrophic gastritis patients, and 724 controls. For the TFF2 rs3814896 polymorphism, in the subgroup aged ≤ 50 years, we found that AG + GG genotypes were associated with a 0.746-fold decreased risk of atrophic gastritis [p = 0.023, 95% confidence interval (CI) = 0.580–0.960], a 0.626-fold decreased risk of GC (p = 0.005, 95% CI = 0.451–0.868), and a 0.663-fold decreased risk of diffuse-type GC (p = 0.034, 95% CI = 0.452–0.970) compared with the common AA genotype. For the TFF3 rs9981660 polymorphism, in the male subgroup, individuals with variant AG + AA genotype were associated with a 0.761-fold decreased risk of diffuse-type GC compared with the common GG genotype (p = 0.043, 95% CI = 0.584–0.992). Additionally, we found that in subjects aged ≤ 50 years compared with common AA genotype, TFF2 rs3814896 AG + GG genotypes were associated with increased TFF2 mRNA levels in the total gastric cancer specimens and in the diffuse-type gastric cancer specimens; and in males aged ≤ 50 years compared with common GG genotype, TFF3 rs9981660 AA + AG genotypes were associated with TFF3 mRNA levels in diffuse-type gastric cancer tissues and their corresponding non-cancerous tissues. To our knowledge, this is the first report of an association between the TFF2 rs3814896 AG + GG genotypes and decreased risks of GC, diffuse-type GC, and atrophic gastritis in younger people aged ≤ 50 years, and an association between TFF3 rs9981660 AG + AA genotype and decreased risk of diffuse-type GC in men. Moreover, we found that TFF2 rs3814896 AG + GG genotypes in people aged ≤ 50 years and TFF3 rs9981660 AG + AA genotypes in younger males with diffuse-type GC were associated with higher levels of TFF2 and TFF3 mRNA respectively.     

The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: A pooled analysis of 41 sets of data from case–control studies

Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR = 0.92, 95%CI = 0.852–0.994, P = 0.034; I² = 0%, P = 0.042; allele analysis: pooled OR = 0.915, 95%CI = 0.874–0.958, P = 0; I² = 0%, P = 0.424; codominant model: OR = 0.835, 95%CI = 0.762–0.916, P = 0; I² = 0%, P = 0.684) and rs1570360/VEGF (recessive model: OR = 0.596, 95%CI = 0.421–0.843, P = 0.003; I² = 23.9%, P = 0.269; codominant model: OR = 0.576, 95%CI = 0.404–0.820, P = 0.002; I² = 49.1%, P = 0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR = 0.834, 95%CI = 0.769–0.904, P = 0; allele analysis: OR = 0.908, 95%CI = 0.863–0.955, P = 0; AA vs CC: OR = 0.829, 95%CI = 0.750–0.916, P = 0; AC vs CC: OR = 0.837, 95%CI = 0.768–0.912, P = 0). In addition, in Asians (allele analysis: OR = 0.21, 95%CI = 0.168–0.262, P = 0) and Caucasians (recessive model: OR = 0.453, 95%CI: 0.240–0.855, P = 0.015; codominant model: OR = 0.464, 95%CI = 0.240–0.898, P = 0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: A meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR = 1.64, 95% CI: 1.02–2.64; GA + GG versus AA, OR = 1.64, 95% CI: 1.00–2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR = 0.37, 95% CI: 0.14–0.98; GG versus GA + AA, OR = 0.37, 95% CI: 0.14–0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR = 1.72, 95% CI: 1.27–2.33; TC versus CC, OR = 1.63, 95% CI: 1.18–2.26; TT + TC versus CC, OR = 1.70, 95% CI: 1.24–2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR = 2.01, 95% CI: 1.40–2.89; TC versus CC, OR = 1.86, 95% CI: 1.26–2.74; TT + TC versus CC, OR = 1.97, 95% CI: 1.35–2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

GSTM1 and GSTT1 gene polymorphisms as major risk factors for bronchopulmonary dysplasia in a Chinese Han population

Bronchopulmonary dysphasia (BPD) is a complex multifactorial disease with an obvious genetic predisposition. Oxidative stress plays an important role in its pathogenesis. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. In the present study, the hypothesis that polymorphisms in the GSTM1 and GSTT1 genes are associated with BPD in Chinese Han infants was examined. Sixty infants with BPD and 100 gestational age and birth weight-matched preterm infants without BPD were recruited. Genotyping for GSTM1 and GSTT1 was performed by multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was more prevalent in BPD infants (65.0%) than in the control subjects (48.0%), which yielded higher risk towards BPD (odds ratio (OR): 2.012, 95% confidence interval (CI) = 1.040–3.892, p = 0.037). There was no statistically significant association of GSTT1 genotype with BPD (OR: 1.691, 95% CI = 0.884–3.236, p = 0.111), although the frequency of GSTT1 null genotype was higher among the BPD subjects (60.0%) than in the control patients (47.0%). GSTM1 and GSTT1 double null genotype was also higher in BPD group (38.3%) than in controls (21.0%) with a higher risk towards BPD (OR: 2.338, 95%CI = 1.151–4.751, p = 0.017). The results suggest that null genotypes of GSTM1 and GSTT1 genes may contribute to the development of BPD in our Chinese Han population.     

An updated meta-analysis of endothelial nitric oxide synthase gene: Three well-characterized polymorphisms with ischemic stroke

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic stroke (IS), but the results are still debatable. A meta-analysis was performed to investigate the association between the eNOS gene polymorphisms in IS risk. Case–control studies on the association between the G894T, T-786C, and 4b/a polymorphisms and IS were searched up to July 2012, and the genotype frequencies in the control group were found to be consistent with the Hardy–Weinberg equilibrium (HWE). The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Meta-regression was used to explore the potential sources of heterogeneity. Funnel plots and Egger's test was used to estimate small study biases, and heterogeneity was assessed by chi-square-based Q-test and I² test. There were total 6537/6475 cases/controls for G894T, 3459/3951 cases/controls for 4b/a, and 2125/2673 cases/controls for T-786C polymorphism. For G894T and 4b/a, a significant association of 894 T allele and 4a allele with increased risk of IS was found in Asians (TT + GT vs. GG: p < 0.00001, OR = 1.60, 95% CI = 1.38–1.79, P_{heterogeneity} = 0.11; aa + ba vs. bb: P < 0.00001, OR = 1.60, 95% CI = 1.30–1.97, P_{heterogeneity} = 0.02), but not in Caucasians (TT + GT vs. GG: P = 0.60, OR = 0.94, 95% CI = 0.75–1.19, P_{heterogeneity} = 0.002; aa + ba vs. bb: P = 0.13, OR = 0.81, 95% CI = 0.62–1.06, P_{heterogeneity} = 0.63). For T-786C polymorphism, there were no significant differences in genotype distribution between IS and control in Asians (CC + TC vs. TT: P = 0.15, OR = 1.14, 95% CI = 0.95–1.37, P_{heterogeneity} = 0.94) and in Caucasians (CC + TC vs. TT: P = 0.72, OR = 0.96, 95% CI = 0.75–1.22, P_{heterogeneity} = 0.53). This analysis provides strong evidence that the eNOS T-786C gene polymorphism is not associated with IS, the G894T and 4b/a polymorphisms might be associated with IS, at least in Asians.     

The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population

Prolactin (PRL) is a hormone–cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism − 1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL − 1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL − 1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case–control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR–RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p = 0.022) and allelic (p = 0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT + TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45–0.92; p = 0.011). The T allele carriers (GT + TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p = 0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1 > 0.72 > 0.19; CS: 1 > 0.54 > 0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL − 1149 T allele is a genetic marker for decreased RA susceptibility and is associated with lower titers of anti-CCP antibodies in Mexican population. We also suggest influence of genotype upon PRL mRNA expression.     

The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

The Val158Met polymorphism of the COMT gene has been implicated in susceptibility to uterine leiomyoma (ULM), but the reported results were inconclusive. The aim of the study was to evaluate the Val158Met polymorphism of the COMT gene and the risk of ULM by meta-analysis. A comprehensive electronic search for relevant articles was conducted in Pubmed, Embase, CNKI, Wanfang, and Weipu databases. Statistical analysis was performed by using the Revman4.2 software and Stata10.0 software. A total of 7 articles including 12 case–control studies were identified in this meta-analysis. The results showed that the polymorphism was associated with decreased risk of ULM (Met/Met + Val/Met vs. Met/Met: OR = 0.84, 95% CI = 0.70–0.99, Z = 2.07, p = 0.04). In the subgroup analyses by ethnicity, significant decreased risk was found among the black populations (OR = 0.68, 95% CI = 0.48–0.97, Z = 2.15, p = 0.03). The current meta-analysis suggested that the Val158Met polymorphism in the COMT gene was associated with decreased risk of ULM, especially in the black population. Future studies are needed to validate our conclusions.     

The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease

Background

Hydroxymethylglutaryl-Coenzyme A Reductase (HMGCR) catalyzes the rate-limiting step of cholesterol biosynthesis. This enzyme is the target of the widely available cholesterol lowering statins. In this population-based case–control study, the frequencies of -911 C>A polymorphism (rs3761740) of the HMGCR gene in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and hypercholesterolemia with cardiovascular risk factors were analyzed.

Methods

The HMGCR genotypes were determined in 365 patients with CHD and 365 controls by PCR–RFLP assay. Anthropometric measurements were measured in all participants.

Results

There was no significant difference in the genotype frequencies of the HMGCR polymorphism between the male subjects of both patient and control groups, however, the HMGCR-CC genotype was found to be more frequent in female patients with CHD than female controls (p = 0.002). The HMGCR-CC genotype showed higher total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels than the CA + AA genotypes in male CHD patients (p = 0.018). Due to this significant sex interaction, a multivariate analysis was conducted on the patient group. In the multivariate logistic regression analysis, the HMGCR-CC genotype was significantly associated with age < 55 (OR = 2.837, p = 0.001) and TC ≥ 5.18 mmol/L (OR = 1.970, p = 0.027) in male subjects. However, this association was not observed in female patients (p > 0.05). This analysis confirmed that the HMGCR-CC genotype was associated with elevated TC levels in male CHD patients with age < 55 years.

Conclusion

These results suggest that age and sex modify the contribution of the HMGCR-911 polymorphism to fasting serum TC, LDL-C levels and risk of CHD.     

Genetic association of interleukin-10 promoter polymorphisms and susceptibility to diffuse large B-cell lymphoma: A meta-analysis

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed, focusing on four major IL-10 gene variants in the promoter region: –3575T/A, –1082A/G, –819C/T and –592C/A. We applied the false discovery rate (FDR) method to adjust for multiple testing. A significant association between IL-10 –3575T/A polymorphism and the risk of DLBCL was observed in the pooled 10 case–control studies (A vs. T: OR = 1.16, 95% CI = 1.08–1.25, P < 0.0001; AA + TA vs. TT: OR = 1.20, 95% CI = 1.08–1.33, P = 0.0009; AA vs. TA + TT: OR = 1.25, 95% CI = 1.09–1.44, P = 0.001). The results indicated that carriers of –1082G allele (–1082GG/GA genotypes) had a nearly 30% increased risk of DLBCL, as compared with carriers of –1082AA genotype (GG + GA vs. AA: OR = 1.30, 95% CI = 1.08–1.57, P = 0.005). When P-values were not adjusted for multiple testing, the risk was significantly decreased among people with –592AA genotype (AA vs. AC + CC: OR = 0.63, 95% CI = 0.43–0.94, P = 0.02), while carriers with –819TT genotype also modestly weakened the DLBCL susceptibility at a marginal level of significance (TT vs. CT + CC: OR = 0.59, 95% CI = 0.35–0.99, P = 0.05). However, these associations were not significant after correction for multiple testing. This meta-analysis suggests that IL-10 –3575A allele confers a greater risk to DLBCL susceptibility, while –1082A/G polymorphism also has significant association with DLBCL risk. These results may help to further clarify the malignancy-risk gene signature of DLBCL, and thus have prognostic and predictive value especially for early-stage DLBCL.     

The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene SG13S114 polymorphism and ischemic stroke in Chinese population: A meta-analysis

Previous studies have indicated that the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene SG13S114 polymorphism is associated with risk of ischemic stroke (IS), but the results remain inconclusive even in Chinese population. A meta-analysis of 10 case-control studies was conducted on the relationship between ALOX5AP SG13S114 polymorphism and susceptibility to IS in Chinese population published domestically and abroad from September 2007 to December 2012. Data were extracted by two authors and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Meta-analysis results showed that the significant association between SG13S114 variant and IS was found under the allelic (OR = 0.87, 95% CI: 0.80–0.96, P = 0.004), dominant (OR = 0.75, 95% CI: 0.62–0.92, P = 0.005), and recessive (OR = 0.89, 95% CI: 0.82–0.97, P = 0.005) genetic models in Chinese population. In subgroup meta-analysis, SG13S114 variant and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the allelic (OR = 0.86, 95% CI: 0.80–0.92, P < 0.0001), dominant (OR = 0.72, 95% CI: 0.57–0.91, P = 0.006), and recessive (OR = 0.86, 95% CI: 0.78–0.95, P = 0.002) models. ALOX5AP SG13S114 polymorphism is associated with susceptibility to IS in Chinese population.     

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.     

Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: A meta-analysis

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs20541 and allergic rhinitis (AR) risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs20541 with AR risk. Eight studies were included in the present meta-analysis (2153 cases and 3931 controls). The combined results based on all studies showed that IL-13 SNP rs20541 was associated with increased AR risk (Gln versus Arg: odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.30; Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.20–1.92; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.19, 95% CI = 1.06–1.33; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.42, 95% CI = 1.13–1.79). When stratifying for race, IL-13 SNP rs20541 exhibited increased AR risk in Asians (Gln versus Arg: OR = 1.20, 95% CI = 1.06–1.36; Gln/Gln versus Arg/Arg: OR = 1.57, 95% CI = 1.17–2.12; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.22, 95% CI = 1.04–1.44; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93), while no significant association was detected in Caucasians (Gln versus Arg: OR = 1.28, 95% CI = 0.93 ~ 1.78; Gln/Gln versus Arg/Arg: OR = 1.42, 95% CI = 0.96–2.11; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.35, 95% CI = 0.89–2.05; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.37, 95% CI = 0.93–2.02). This meta-analysis supported that IL-13 SNP rs20541 was associated with AR, particularly in Asians.