Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk

Background: The GRK4 and EMILIN1 genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk.Methods: Published literature from PubMed and Embase databases were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model.Results: Five studies for polymorphisms in the GRK4 gene and five studies for polymorphisms in the EMILIN1 gene were identified. The results suggested that rs1801058 polymorphism in the GRK4 gene was inversely associated with hypertension among East Asians (TT vs. CC: OR=0.39, 95%CI 0.28-0.55) and positively associated with hypertension among Europeans (TT vs. CC: OR= 2.38, 95%CI 1.38-4.10). Rs2960306 polymorphism in the GRK4 gene was significantly associated with hypertension among Europeans (TT vs. GG: OR=1.92, 95%CI 1.13-3.27). The significant associations were also observed for rs2011616 and rs2304682 polymorphisms in the EMILIN1 gene among Japanese (rs2011616: AA vs. GG: OR=0.38, 95%CI 0.18-0.82; rs2304682: GG vs. CC: OR=0.37, 95%CI 0.17-0.81) but not among Chinese.Conclusions: This meta-analysis suggested that rs1801058 polymorphism in the GRK4 gene was associated with hypertension in East Asians and Europeans. The significant association was also found for rs2960306 polymorphism in the GRK4 gene among Europeans. In addition, there were significant associations of rs2011616 and rs2304682 polymorphisms in the EMILIN1gene with hypertension among Japanese.     

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

Pseudoexfoliation (PEX) is an age‐related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic‐based meta‐analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06–0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02–0.06) and Koreans (OR = 0.10, 95%CI:0.05–0.22). These associations we‐re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22–17.41) and Koreans (OR = 6.63, 95%CI:2.60–16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.     

Association of the Vascular Endothelial Growth Factor Gene Polymorphisms (–460C/T, +405G/C and +936T/C) with Endometriosis: A Meta‐Analysis

Published data on the association between the vascular endothelial growth factor (VEGF) gene –460C/T (rs833061), +405G/C (rs2010963), +936T/C (rs3025039) polymorphisms and endometriosis risk are inconclusive. Eleven eligible case‐control studies including 2690 cases and 2803 controls were included in this meta‐analysis through searching the databases of PubMed and CBMdisc (up to August 1, 2011). In the overall analysis, no significant association between the –460C/T and +405G/C polymorphisms and risk of endometriosis was observed. However, significant associations were observed between endometriosis risk and VEGF+936T polymorphism with summarized odds ratio of 1.19 (95%CI, 1.02–1.37), 1.18 (95%CI, 1.03–1.37), 1.15 (95%CI, 1.01–1.30) for CT versus CC genotype, dominant mode (CT/TT vs. CC) and allele comparison (T vs. C), respectively. Furthermore, stratified analysis showed that significantly strong association between +936T/C polymorphism and endometriosis was present only in stage III–IV (OR = 1.32 for dominant mode; OR = 1.30 for T vs. C), but not in stage I–II. However, no significantly increased risk of endometriosis was found in any of the genetic models in Asians or in Caucasians. This meta‐analysis supports that VEGF+936T/C polymorphism is capable of causing endometriosis susceptibility.     

Association between interferon lambda 3 rs12979860 polymorphism and clinical outcome in dengue virus‐infected children

Single nucleotide polymorphisms (SNPs) in immune‐related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue‐related symptoms (aged 1–15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV‐infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98–3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07–3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08–0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN‐λ expression and DENV immunopathogenesis.     

Genetic variation in LINGO-1 (rs9652490) and risk of Parkinson's disease: Twelve studies and a meta-analysis

Studies of the relationship between Parkinson's disease (PD) and rs9652490 SNP in LINGO1 gene have reported inconsistent results. To assess the association between the variant and PD risk, a meta-analysis from 12 case–control studies was performed. A total of 6053 PD cases and 5997 controls in 4 studies among Asians and 8 studies among non-Asians were included. The overall and geographic subgroups analysis was conducted, and odds ratios (OR) and 95% confidence intervals (95%CI) were calculated in the fixed-effects or random-effects model. The combined results of overall analysis showed a lack of association of rs9652490 and PD (fixed-effects model, OR 1.00, 95%CI 0.94–1.06), no matter what genetic model of rs9652490. The separate analysis in patients of Asian origin or non-Asian origin also failed to show any ethnic-dependent association. In conclusion, the present meta-analysis does not support the notion that LINGO1 rs9652490 SNP is a major genetic risk factor for PD.     

Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta‐analysis

Candidate gene as well as genome‐wide association studies identified several polymorphic variants to be associated with lung cancer worldwide including in India. However, contradictory results have failed to estimate the overall effect of the polymorphic variants on the disease. Textmining was conducted on PubMed following specific search strings to gather all the publications related to genetic association with lung cancer in India. Out of 211 PubMed hits only 30 studies were selected for meta‐analysis following specific inclusion criteria. Heterogeneity between studies was calculated by Cochran's Q‐test (P < 0.05) and heterogeneity index (I²). Publication bias was visualized by funnel plots and Egger's regression test. For each variant, following a fixed‐effect model, summary odds ratio (OR) along with 95% confidence interval (CI) was estimated. The meta‐analysis revealed three polymorphic variants viz. ‘deletion polymorphism (del1) (OR = 1.39, 95% CI = 1.03–1.87, P = 0.027) in GSTT1’, ‘deletion polymorphism (del2) (OR = 1.30, 95% CI = 1.01–1.67, P = 0.038) in GSTM1’ and ‘rs1048943 (OR = 1.98, 95% CI = 1.27–3.10, P = 0.002) in CYP1A1’ to be associated with lung cancer. However, after multiple testing correction, only rs1048943 was found to be significantly associated (P value = 0.0321) with lung cancer. None of the polymorphic variants showed any evidence of heterogeneity between studies or of publication bias. Our meta‐analysis revealed strong association of rs1048943 in CYP1A1, but a suggestive association of deletion polymorphisms in GSTT1 and GSTM1 with lung cancer, which provides a comprehensive insight on the overall effect of the polymorphic variants, reported in various case–control studies on Indian population, on the risk of lung cancer development. Environ. Mol. Mutagen. 58:688–700, 2017. © 2017 Wiley Periodicals, Inc.     

JAK2 rs10758669 Polymorphisms and Susceptibility to Ulcerative Colitis and Crohn's Disease: A Meta-analysis

In this meta-analysis, we aimed to clarify the impact of Janus kinase 2 (JAK2) rs10758669 polymorphisms on ulcerative colitis (UC) and Crohn's disease (CD) risk. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 %CIs) were calculated. Eleven studies with 7009 CD patients, 7929 UC patients, and 19235 controls were included. The results showed that JAK2 rs10758669 polymorphism was associated with CD (AC vs. AA, OR?=?1.16, 95 %CI, 1.08–1.24; CC vs. AA, OR?=?1.29, 95 %CI, 1.17–1.43; AC?+?CC vs. AA, OR?=?1.19, 95 %CI, 1.11–1.27; CC vs. AA?+?AC, OR?=?1.19, 95 %CI, 1.09–1.31; C vs. A, OR?=?1.14, 95 %CI, 1.09–1.20) and UC susceptibility (AC vs. AA, OR?=?1.14, 95 %CI, 1.06–1.22; CC vs. AA, OR?=?1.33, 95 %CI, 1.20–1.47; AC?+?CC vs. AA, OR?=?1.18, 95 %CI, 1.10–1.27; CC vs. AA?+?AC, OR?=?1.24, 95 %CI, 1.12–1.36; C vs. A, OR?=?1.15, 95 %CI, 1.10–1.21). But no significant association was found between JAK2 rs10758669 polymorphism with CD in Asian. Either in adult-onset group or multi-age group, hospital-based group or population-based group, JAK2 rs10758669 polymorphism was associated with CD and UC susceptibility. This meta-analysis indicated that JAK2 rs10758669 polymorphism was a risk factor both for CD and UC, especially in Caucasian. The differences in age of onset and study design did not influence the associations obviously. Gene–gene and gene–environment interactions should be investigated in the future.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss

Some case-control studies have demonstrated that caffeine intake and high CYP1A2 activity increase risks of recurrent pregnancy loss (RPL) but the multifactorial effect is obscure. To investigate whether susceptible women who have more caffeine intake are at high risk of RPL, a case-control study of 58 cases with two or more RPL and fertile 147 controls was performed. The association between daily caffeine intake together with CYP1A21F (AA versus CA and CC) genotype and RPL was assessed. Without consideration of the genotype, there were no significant differences of the RPL risk in proportion to daily caffeine intake [less than 100 mg (reference); 100-299 mg: odds ratio (OR), 1.29; 95% confidence interval (CI), 0.66-2.50; 300 mg or more: OR, 1.82; 95% CI, 0.72-4.58; P for trend, 0.20]. However, the RPL risk significantly increased only among women who had homozygous CYP1A21F alleles with a dosage effect of daily caffeine intake [less than 100 mg (reference); 100-299 mg: OR, 1.94; 95% CI, 0.57-6.66; 300 mg or more: OR, 5.23; 95% CI, 1.05-25.9; P for trend, 0.03]. It was demonstrated for the first time that an increase in caffeine intake deteriorates the fecundity among susceptible women.     

Polymorphisms in IL‐1A are associated with endometrial cancer susceptibility among Chinese Han population: A case–control study

Endometrial cancer (EC) is one of the most common malignant tumours of the female genital tract, and it has become a serious malignant disease of the female genital tract in China. Existing researches have revealed the association between polymorphisms of IL‐1A and several gynaecological diseases. In this research, we analysed the association between IL‐1A gene polymorphisms and endometrial cancer susceptibility in Chinese female population. A total of 81 patients and 198 healthy people were selected. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. Genetic models and analyses showed that IL‐1A rs3783550 TT and rs3783546 CC increased the risk of endometrial cancer under the recessive model, respectively (rs3783550: OR = 2.80, 95%CI: 1.32–5.92, p = .008; rs3783546: OR = 2.79, 95%CI: 1.32–5.89, p = .008). In the recessive model, we also found that both IL‐1A rs1609682 and IL‐1A rs3783521 increased the risk of endometrial cancer, respectively (rs1609682: OR = 2.79, 95%CI: 1.32–5.89, p = .0081; rs3783521: OR = 2.80, 95%CI: 1.32–5.92, p = .008). Haplotype analysis was performed that did not reveal any significant results. In summary, IL‐1A rs3783550, rs3783546, rs1609682 and rs3783521 polymorphisms may be associated with an increased risk of endometrial cancer in Chinese female populations.     

The PD-1 rs36084323 A > G polymorphism decrease cancer risk in Asian: A meta-analysis

The rs36084323 A?>?G polymorphism in programmed cell death-1(PD-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to identify the potential association, by searching the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI, WANFANG and CBM databases. Data were extracted and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the strength of the association. A total of 10 relevant studies involving 4445 cancer cases and 5126 controls were recruited. Overall, the results indicated that the PD-1 rs36084323 A?>?G polymorphism was not statistically associated with cancer risk. However, stratified analysis revealed that there was a statistically reduced cancer risk in Asians(G vs. A, OR?=?0.89, 95%CI:0.81–0.97, P?=?0.008, I²?=?48.8%; GG vs. AA, OR?=?0.79, 95% CI:0.66–0.94, P?=?0.008, I²?=?48.7%; GG/AG vs. AA, OR?=?0.87, 95%CI:0.76–0.98, P?=?0.017, I²?=?34.9%; GG vs. AG/AA, OR?=?0.85, 95%CI:0.75–0.97, P?=?0.027, I²?=?40%) and in the patients with EOC(AG vs. AA, OR?=?0.69, 95%CI:0.54–0.90, P?=?0.005, I²?=?0%; GG/AG vs. AA, OR?=?0.67, 95%CI:0.52–0.85, P?=?0.001, I²?=?0). Meta-regression showed that ethnicity (P?=?0.029) but not cancer types (P?=?0.792), source of controls (P?=?0.207) or ample size (P?=?0.585) were the sources of heterogeneity. This meta-analysis demonstrates the PD-1 rs36084323 A?>?G polymorphism is associated with decreased cancer risk in Asian, and suggests it could potentially serve as a biomarker to screen high-risk individuals. Large-scale and well-designed case-control studies are needed to enrich the evidence of this result.     

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.     

Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA-4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case–control study. Four single nucleotide polymorphism sites of CTLA-4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism ‘TC’ genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35–.63), p < .001]. GC cases with dominant genetic model ‘TC + CC’ had a 47% reduced risk of GC [OR, 95%CI: .53 (.40–.71), p < .001]. Subgroup analyses revealed that the rs733618 ‘TC + CC’ genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31–.58), p < .001], those aged ≤60 years old [OR, 95%CI: .27 (.18–.42), p < .001], non-drinkers [OR, 95%CI: .21 (.13–.33), p < .001], non-smokers [OR, 95%CI: .38 (.25–.57), p < .001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10–.26), p < .001]. Further multivariated analyses indicated that individuals with the ‘TC + CC’ rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29–.83), p = .032] and had no H. pylori infection [OR, 95%CI: .35 (.28–.76), p = .018] were found to have a protective effect against GC. Additionally, soluble CTLA-4 were significantly lower in GC patients with ‘TC’ and ‘TC + CC’ genotypes (all p < .05). Our findings suggest that the rs733618 polymorphism of CTLA-4 gene may play a critical role in the prevention of GC.     

Recurrent Pregnancy Loss and Apolipoprotein E Gene Polymorphisms: A Case–Control Study from North India

Citation Agarwal M, Parveen F, Faridi RM, Phadke SR, Das V, Agrawal S. Recurrent pregnancy loss and apolipoprotein E gene polymorphisms: a case–control study from North India. Am J Reprod Immunol 2010; 64: 172–178 Problem The role of apolipoprotein E gene polymorphisms in the etiology of recurrent pregnancy loss (RPL) is not clearly understood. We evaluated this polymorphism in unexplained pregnancy losses among North Indian women. Method of study In a retrospective case–control study, 200 well‐characterized RPL cases were examined for their APO‐E genotypes based on restriction fragment length polymorphism analysis of PCR‐amplified fragments including amino acid positions 112 and 158. The observed genotypes were compared with those obtained from an equal number of ethnically matched negative controls. Results We found similar APO‐E genotypes and E2, E3, and E4 allele frequency distribution among RPL patients and controls. The allele frequencies obtained in patients and controls respectively were as follows: E2 = 7.5% and 9.0% (P = 0.52; OR = 0.81; 95%CI = 0.49–1.35), E3 = 89.7% and 90% (P = 1.00; OR = 0.97; 95%CI = 0.61–1.54), and E4 = 2.8% and 1% (P = 0.12; OR = 2.79; 95%CI = 0.88–8.86). Conclusions Our data did not support the association of APO‐E gene polymorphisms with recurrent pregnancy loss as reported by some of the previous studies. We endorse adequate characterization of RPL cases, inclusion of appropriate negative controls, and adequate sample size prior to addressing such studies.     

Association of SUMO4 M55V polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis

The purpose of this study was to generate large-scale evidence on whether SUMO4 M55V polymorphism is associated with autoimmune and inflammatory diseases using a meta-analysis. We surveyed studies on the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in PubMed. Meta-analysis was performed for genotypes AG versus AA, GG versus AA, GG versus AA + AG, AG + GG versus AA and G allele versus A allele in a fixed/random effect model. We identified 16 studies (11 407 cases and 10 679 controls) using PubMed search. When all groups were pooled, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases (G versus A: OR = 1.11, 95%CI = 1.03–1.19, P = 0.005; AG + GG versus AA: OR = 1.17, 95%CI = 1.06–1.28, P = 0.001; GG versus AA + AG: OR = 1.07, 95%CI = 0.94–1.21, P = 0.29; GG versus AA: OR = 1.15, 95%CI = 1.00–1.34, P = 0.06; AG versus AA: OR = 1.15, 95%CI = 1.08–1.23, P < 0.0001). In subgroup analyses, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in Asian population (G versus A: OR = 1.18, 95%CI = 1.08–1.28, P = 0.0001; AG + GG versus AA: OR = 1.30, 95%CI = 1.16–1.45, P < 0.00001; GG versus AA + AG: OR = 1.04, 95%CI = 0.78–1.37, P = 0.80; GG versus AA: OR = 1.20, 95%CI = 0.99–1.45, P = 0.07; AG versus AA: OR = 1.32, 95%CI = 1.18–1.49, P < 0.00001). But the association was not found in Caucasian population. Meanwhile, an association of SUMO4 M55V polymorphism with autoimmune diabetes was found (G versus A: OR = 1.18, 95%CI = 1.08–1.30, P = 0.0005; AG + GG versus AA: OR = 1.22, 95%CI = 1.13–1.32, P < 0.00001; GG versus AA + AG: OR = 1.15, 95%CI = 0.96–1.38, P = 0.13; GG versus AA: OR = 1.32, 95%CI = 1.08–1.60, P = 0.006; AG versus AA: OR = 1.23, 95%CI = 1.13–1.33, P < 0.00001). This meta-analysis demonstrates the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases, especially in Asian population.     

CASP3和 CASP9基因多态性与胃癌遗传易感性的关联研究

目的 探讨凋亡相关基因caspase 3 (CASP3)、caspase 9 (CASP9)单核苷酸多态性与胃癌遗传易感性的关系.方法 采用以自然人群为基础的病例对照研究设计,对278例胃癌患者和以同年龄(± 5岁)、同性别、同居住地匹配为原则获得的278名对照进行研究.CASP3 rs12108497和 CASP9 rs4646018多态位点的基因分型采用聚合酶链反应-限制性片段长度多态性的方法分析.非条件Logistic回归分析计算基因多态与胃癌风险的相关性.结果 携带 CASP3 rs12108497 TC、CC基因型者患胃癌的风险较TT基因型者分别增加45%(OR=1.45,95%CI:1.01～2.07)和117% (OR=2.17,95%CI:1.15～4.08).未发现 CASP9 rs4646018基因多态与胃癌发病风险间存在显著关联.多基因模型显示携带1个或2个风险基因型的个体胃癌易感性增高(OR=1.60,95%CI:1.12～2.30).分层分析表明,携带1个或2个风险基因型的个体罹患胃癌的危险度在男性个体(OR=1.62,95%CI:1.05～2.49)、吸烟者(OR=1.87,95%CI:1.12～3.12)、饮酒者(OR=1.92,95%CI:1.02～3.65)和无肿瘤家族史者(OR=1.78,95%CI:1.18～2.68)中尤为明显.结论 CASP3 rs12108497 多态性会增加胃癌的发病风险.CASP9 rs4646018多态性与胃癌发病风险无关.

Abstract：

Objective To investigate the association between the apoptosis genes CASP3 (rs12108497) and CASP9 (rs4646018) polymorphisms and the risk of developing stomach cancer. Methods In this population-based case-control study, 278 cases with stomach cancer and 278 age (±5 years), gender, and residential area matched controls were recruited. The genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The unconditional Logistic regression analysis was utilized to calculate the odds ratios (OR) and 95% confidence intervals (CI). Results The individuals with TC, CC genotypes of rs12108497 locus had significantly increased risk of stomach cancer in comparison to those carrying TT genotype (OR=1.45, 95% CI: 1.01-2.07 for TC; OR=2.17, 95%CI: 1.15-4.08 for CC). However, the rs4646018 locus of CASP9 gene polymorphism was not related to stomach cancer risk. Compared with the subjects carrying the both low-risk genotypes, those carrying 1 or 2 high-risk genotypes had a noteworthy increased risk of stomach cancer (OR=1.60, 95% CI: 1.12-2.30). The combined high-risk genotypes appeared to be more evident in subjects of male (OR=1.62, 95% CI: 1.05-2.49), ever-smokers (OR=1.87, 95%CI: 1.12-3.12), ever-drinkers (OR=1.92, 95%CI:1.02-3.65) and no family history of cancer (OR=1.78, 95%CI: 1.18-2.68). Conclusion The current findings suggest that the polymorphism of CASP3 rs12108497 might be associated with the risk of stomach cancer. However, the CASP9 rs4646018 polymorphism may not be related to the stomach cancer risk.     

Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population

Centrosome defects can result in aneuploidy and genomic instability, and have important implications for breast cancer development. The Aurora-A and BRCA1 proteins interact and both are strongly involved in centrosome regulation. Genetic variants in these two genes may have an effect on breast cancer development. Here, we report a comprehensive single nucleotide polymorphism (SNP) and haplotype-tagging association study on these two genes in 1334 breast cancer cases and 1568 unaffected controls among the Chinese Han population. Apart from a missense SNP, rs2273535 (Phe31Ile), and a probable risk SNP, rs2064863, six htSNPs were analysed in three high-LD blocks of AURKA spanning from 10 kb upstream to 2 kb downstream of AURKA. For BRCA1, six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end of BRCA1). The results showed that four SNPs in AURKA (data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03-4.66, p = 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18-0.82, p = 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18-2.00, p = 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47-0.98, p = 0.0380) and one SNP in BRCA1 (rs3737559, dominant model OR = 1.35, 95% CI = 1.11-1.64, p = 0.0030) were associated with breast cancer susceptibility. After correction for multiple comparisons (FDR = 0.05), only rs6024836 and rs3737559 remained significant. Two haplotypes (CC of block 2, OR = 20.74, 95% CI = 4.35-98.88, p = 0.0001; GG of block 3, OR = 1.32, 95% CI = 1.12-1.56, p = 0.0010) and one diplotype (AG-GG of block 3, OR = 1.63, 95% CI = 1.18-2.26, p = 0.0031) within AURKA showed strong associations with breast cancer risk. One haplotype of BRCA1 (CTGTTG, OR = 1.30, 95% CI = 1.06-1.59, p = 0.0118) was also associated with breast cancer risk. However, women harbouring both at-risk genotypes of Aurora-A and BRCA1 were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in the AURKA and BRCA1 genes may contribute to breast cancer development.     

CYP19A1基因 R264C在中国上海BRCA1/2基因突变阴性的遗传倾向乳腺癌中的作用

目的研究CYP19A1基因R264C的（C→T）单核苷酸多态性基因型在上海地区BRCA1／BR-CA2基因突变阴性的遗传倾向乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法对114例无BRCA1／2突变的家族性／早发性乳腺癌患者和121名正常对照者进行CYP19A1基因第7外显子的聚合酶链反应扩增，随后进行DNA直接测序鉴定其R264C的单核苷酸多态性基因型，比较基因型分布和发病风险的关系；危险度比值比（odd ratio，OR）及95％可信区间（confidence interval，CI）应用非条件Logistie回归分析计算。结果CYP19A1基因R264C多态的CC、CT、TT基因型在病例组中的分布频率分别为84（77．8％），22（20．4％），2（1、8％）；在对照组的分布频率分别为87（77．7％），24（21、4％），1（0．9％）；在研究的总人群中，CT基因型的频率为20．9％（46／220），TT基因型的频率为1．4％（3／220）。以CC基因型为参照，CT或TT基因型没有显著性地提高乳腺癌的发病危险，其中携带CT基因型风险为（OR=1．16，95％CI：0．53。2．55），携带TT基因型风险为（OR=1．44，95％CI：0．12-17．15）；经过月经状态和身体质量指数分层，也未能发现其与乳腺癌发病的相关性。结论CYP19A1基因R264C的单核苷酸多态性在中国汉族人群中的分布有别于其他种族，有其自身的分布特点；R264C可能与上海地区中国汉族人群乳腺癌发生的遗传易感性无关，尚不足作为低外显率的乳腺癌易感基因位点，不建议作为未来临床基因筛查的候选指标。     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

IL3 rs40401 Polymorphism and Interaction with Smoking in Risk of Asthma in Japanese Women: The Kyushu Okinawa Maternal and Child Health Study

Three previous genetic association studies conducted in Korea and China investigated the relationship between IL3 single nucleotide polymorphism (SNP) rs40401 and asthma, but their results were inconsistent. We examined this relationship and the possibility of an interaction between IL3 SNP rs40401 and smoking in young adult Japanese women. Included were 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma. Control subjects were 700 women without asthma according to the ECRHS criteria who had not been diagnosed with asthma and/or allergic rhinitis by a doctor and/or who had not met the criteria of the International Study of Asthma and Allergies in Childhood for rhinoconjunctivitis. A significant positive association was found between SNP rs40401 and the risk of asthma, with the TT genotype as the reference under the additive model: the adjusted odds ratio was 1.39 (95% CI: 1.004–1.93). The positive association was not statistically significant in any other genetic model. Compared with subjects with the TT or TC genotype of SNP rs40401 who had never smoked, those with the CC genotype who had ever smoked had a significantly increased risk of asthma: the adjusted OR was 2.67 (95% CI: 1.23–5.79); the additive interaction, but not the multiplicative interaction, was significant. This study suggests that IL3 SNP rs40401 is significantly associated with the risk of asthma in young adult Japanese women and reveals that the combination of ever smoking and having the CC genotype of IL3 SNP rs40401 is significantly positively associated with asthma.