IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population

Background

The interleukin-23 receptor (IL-23R) plays an important role in the T-helper 17 cell-mediated inflammatory process and is also involved in tumor immune surveillance, which may be linked to carcinogenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In this study, we hypothesized that potentially functional genetic variants of the IL-23R gene may modify HCC risk.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) of IL-23R, rs6682925 and rs1884444, in a case–control study of 837 HCC cases, 899 HBV surface antigen (HBsAg)-positive controls, and 743 HBsAg-negative controls. A reporter gene assay was performed to evaluate the functional relevance of the rs6682925 SNP located at the promoter region of the IL-23R gene.

Results

We found that the two SNPs were associated with the risk of HCC when compared with both the HBsAg-positive and -negative controls. When compared with all controls, IL-23R rs6682925 and rs1884444 both increased the HCC risk in a recessive genetic model [rs6682925 CC vs. TT/TC: odds ratio (OR) 1.35, 95 % confidence interval (CI) 1.07–1.70; rs1884444 GG vs. TT/TG: OR 1.36, 95 % CI 1.05–1.77]. Furthermore, the variant C allele of rs6682925 in the promoter region of IL-23R was associated with increased reporter gene activity.

Conclusions

These findings indicate that genetic variants in IL-23R may contribute to HCC development.     

Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis

Up to now, many publications have evaluated the correlation between IL-23R polymorphisms and ankylosing spondylitis with conflicting results. We perform this meta-analysis to collect all the relevant studies up to date to further clarify the association of IL-23R polymorphisms with AS. Relevant published data were retrieved through Medline, PubMed, Embase, Web of Science, CNKI, Chinese BioMedical Literature Database on disc, and the statistical analysis was conducted using Stata 11.0. (1) A total of 11 literatures, including 13 population samples, were studied. (2) The allele A frequency of rs11209032 was higher in the AS group than in the controls (A vs. G: OR = 1.173, 95% CI = 1.107-1.243, P < 0.001). (3) The allele A of rs1004819 was higher in the AS group than in the controls in both all-pooled population (A vs. G: OR = 1.147, 95% CI = 1.022-1.287, P = 0.02) and Europe-pooled population (A vs. G: OR = 1.199, 95% CI = 1.007-1.429, P = 0.042). (4) The allele frequency T of rs1343151, G of rs10489629, and A of rs11209026 was lower in the AS group than in the controls. (5) No significant differences were found in allele frequency of rs10889677 polymorphism between cases and controls by random effects model. We concluded that the genetic susceptibility for AS is associated with the IL-23R gene polymorphisms. The protective SNPs include rs1343151, rs10489629, and rs11209026 while rs1004819 and rs11209032 may be the susceptibility SNPs.     

Gene–gene interaction between CD40 and CD226 gene on systemic lupus erythematosus in the Chinese Han population

The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene–gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case–control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs. Logistic regression analysis showed that SLE risk was significantly higher in carriers of T allele of rs4810485 in CD40 gene than those with GG genotype (GT+ TT vs GG), adjusted OR (95 % CI) 1.84 (1.40–2.29). In addition, we also found SLE risk was also significantly higher in carriers of rs763361 T allele within CD226 gene than those with CC genotype (CT+ TT vs CC), adjusted OR (95 % CI) 1.89 (1.38–2.13). GMDR analysis suggested a potential gene–gene interaction between rs4810485 and rs763361. Overall, cross-validation consistency of the two-locus model was 10/10, and the testing accuracy was 62.17 %. We also found that subjects with GT or TT of rs4810485 and CT or TT of rs763361 genotype have the highest SLE risk, compared with subjects with GG of rs4810485 and CC of rs763361 genotype, and OR (95 % CI) was 2.14 (1.67–3.08), after covariates adjustment. Our results support an important association of rs4810485 in CD40 gene and rs763361 in CD226 gene polymorphism, combined effect of rs4810485 and rs763361 with increased risk of SLE.     

Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity

CONTEXT: IL-23 and its receptor (IL-23R) guide T cells toward the T-helper 17 phenotype. IL-23R single nucleotide polymorphisms (SNPs) have been associated with several autoimmune diseases, including Crohn's disease and rheumatoid arthritis. OBJECTIVE: Our objective was to determine whether variants in the IL-23R gene are associated with Graves' disease (GD) and Graves' ophthalmopathy (GO). DESIGN AND PARTICIPANTS: A total of 216 North American Caucasian GD patients and 368 healthy controls were genotyped for four SNPs spanning the IL-23R gene. SNPs rs11209026 and rs7530511 were genotyped using the TaqMan allelic discrimination assays (Applied Biosystems, Foster City, CA), and SNPs rs2201841 and rs10889677 were genotyped using a fluorescent-based restriction fragment length polymorphism method. RESULTS: The A allele of rs2201841 was present in 78.8% of GD patients with GO and 64.7% of controls [P=1.1x10(-4); odds ratio (OR)=2.04]; the AA genotype was also significantly increased in GO patients compared with controls (62.5 and 41%, respectively; P=1.0x10(-4); OR=2.4). The C allele of rs10889677 was present in 78.6% of GO patients and 64.5% of controls (P=1.3x10(-4); OR=2.03), and the CC genotype was also significantly increased in GO patients vs. controls (62.1 and 41.0%, respectively; P=1.4x10(-4); OR=2.36). The TT genotype of rs7530511 was significantly associated with GD, but not specifically with GO; it was present in 2.5% of GD patients and 0.3% of controls (P=0.02; OR=9.4). The rs11209026 SNP, which is the most strongly associated with Crohn's disease, was not associated with GD or GO in our data set. CONCLUSIONS: Variants in the IL-23R gene are strongly associated with GO. These variants may predispose to GO by changing the expression and/or function of IL-23R, thereby promoting a proinflammatory signaling cascade.     

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

Abstract

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case–control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) ?1722T/C, CTLA-4 ?318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36–0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39–0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66–0.83; T vs. G: OR 0.72, 95% CI 0.66–0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.     

白细胞介素-23受体基因多态性与中国江苏地区汉族炎症性肠病的关系

目的 研究中国江苏汉族人群炎症性肠病(IBD)发病易感性和白细胞介素-23受体(IL-23R) rs1004819、rs1495965、rs1884444、rs2201841、rs6677188、rs7517847、rs7530511、rs10489629、rs10889677、rs11209026位点单核苷酸多态性(SNP)间的关系。方法 采用多重SNaPshot SNP分型技术,检测134名健康志愿者、135例溃疡性结肠炎(UC)和43例克罗恩病(CD)患者的基因多态性。实验数据使用SPSS 17.0软件进行分析。结果 UC组rs7530511位点CC基因型频率、CT基因型频率、C等位基因频率、T等位基因频率分别为99.26％(134/135)、0.74％(1/135)、99.63％(269/270)、0.37％(1/270),正常对照组则分别为94.03％(126/134)、5.97％(8/134)、97.01％(260/268)、2.99％(8/268),两组基因型频率比较P＝0.040、OR＝0.118、95％CI:0.014～0.953,两组等位基因频率比较P＝0.043、OR＝0.121、95％CI:0.015～0.973。在rs6677188野生型和突变型的UC患者中,各年龄段的分布比例不同,突变型者中青年患者较多,野生型者中中年患者较多,P值分别＝0.032和0.001。UC患者中rs6677188 AT基因型者多处于内镜缓解期(P＝0.032)。结论 IL-23R rs7530511位点突变是UC的保护性因素。rs6677188多态性与患者年龄和内镜下缓解与否有关。     

Lysosomal acid lipase gene single nucleotide polymorphism and pulmonary tuberculosis susceptibility

BackgroundThe factors that predispose to pulmonary tuberculosis (PTB) are not fully understood, However. Gene polymorphisms have been associated with PTB development.ObjectivesIn this study, we investigated the relationship between LIPA gene polymorphisms and a predisposition to pulmonary tuberculosis caused by Mycobacterium tuberculosis.MethodsA total of 202 cases of PTB and 218 healthy controls (HCS) were included in this study. Analyses were done under allelic, homozygous, and heterozygous, dominant, recessive models, and were used to calculate values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. Genotyping was conducted using the real time polymerase chain reaction with high resolution melting curve analysis.ResultsWhen comparing PTB patients with healthy controls (HCS), significant associations with disease development were observed for both SNPs rs1051338 and rs7922269. Analysis was done based on models of genetic inheritance in man that is co-dominant, recessive and dominant models. Rs1051338, the heterozygous (AC vs. AA) P: 0.001, OR: 1.998, 95% CI: 1.312–3.042 and homozygous (CC vs. AA) P: < 0.001, OR: 4.078, 95% CI: 2.134–7.796 Co-dominant associated with increased risk for the disease. Under recessive (CC vs. AA + AC), P: 0.001, OR: 2.829: 95% CI: 1.543–5.185 and dominant model (AC + CC vs. AA) P: < 001, OR: 2.331, 95% CI: 1.564–3.474 the genotypes distribution increased the individual risk, plus its alleles distribution (P: < 0.001, OR: 2.004, 95% CI: 1.505–2.669). Considering SNP rs7922269 mutation significantly increased pulmonary tuberculosis risk as was observed in the homozygous GG vs. TT (P: 0.003, OR: 3.162, 95% CI: 1.431–6.989); heterozygous GT vs. TT (P: < 0.001, OR: 1.2.259, 95% CI: 1.503–3.394); dominant model (GT + GG vs. TT; P: < 0.001, OR: 2.061, 95% CI: 1.402–3.032) and the allele G (P: < 0.001, OR: 1.829, 95% CI:1.361–2.458), however no significant association was observed in the Recessive model (GG vs. TT + GT; P: 0.057, OR: 2.568, 95% CI: 0.965–4.432).ConclusionThe findings of our study strengthen the hypothesis that LIPA rs1051338 and rs7922269 polymorphism associated with increased risk for pulmonary Tb in a sample of northern Chinese population.     

Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus

Introduction and objectivesConsidering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population.Materials and methodsA case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique.ResultsAnalysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility.ConclusionThese findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE.     

Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene

Background

Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity.

Methods

The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.

Results

The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09–2.05, p = 0.012; and OR 1.51, 95 % CI 1.09–2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10–2.17, p = 0.013; and OR 1.56, 95 % CI 1.10–2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01–2.21, p = 0.044; and OR 1.52, 95 % CI 1.03–2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28–5.43, p = 0.009; and OR 4.35, 95 % CI 1.93–9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41–12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08–2.85, p = 0.04).

Conclusion

This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.     

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG?+?GG: OR 0.48, 95% CI 0.39-0.59; TT?+?TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.     

Association of adiponectin gene polymorphisms and additional gene-gene interaction with nonalcoholic fatty liver disease in the Chinese Han population

Purpose

To investigate the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene and nonalcoholic fatty liver disease (NAFLD) as well as the impact of the interaction of multiple SNPs on NAFLD risk, based on a Chinese population study.

Methods

A total of 612 subjects (411 male, 201 female) were selected, including 302 NAFLD patients and 310 controls. Three SNPs were selected for genotyping in the case-control study: rs266729, rs822393, and rs1501299. A logistic regression model was used to examine the interaction between the SNPs and NAFLD. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction among SNPs.

Results

Logistic analysis showed a significant association between genotypes of variants in rs266729 and rs822393 and increased NAFLD risk. The carriers of the homozygous mutant of two SNP polymorphisms revealed increased NAFLD risk compared to those with wild-type homozygotes; ORs (95 % CI) were 1.31 (1.14–1.81) (p = 0.001) and 1.18 (1.05–1.71) (p = 0.005), respectively. There was a significant two-locus model (p = 0.0010) involving rs266729 and rs822393, indicating a potential gene-gene interaction between rs266729 and rs822393. Overall, the two-locus models had a cross-validation consistency of 10 and testing accuracy of 62.17 %. Subjects with the CG or GG and CT or TT genotype have the highest NAFLD risk compared to subjects with the CC-CC genotype; the OR (95 % CI) was 2.52 (1.31–3.82), p < 0.001, after covariate adjustment.

Conclusions

Our results support an important association of the rs266729 (?11377 G/C) and rs822393 (?4522 C/T) polymorphism with increased risk of NAFLD. The interaction analysis showed a combined effect of rs266729 and rs822393 on NAFLD.

     

The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies

Numbers of observational studies suggest that the JAK2 46/1 (GGCC) haplotype may increase the risk of myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT), but the results remain controversial. We aimed to examine the association between the JAK2 46/1 haplotype and risk of MPNs and SVT by conducting a meta-analysis. PubMed, EMBASE, Cochrane Library, CBM, and CNKI databases were searched to identify eligible studies without restrictions and by reviewing reference lists of obtained articles. Both fixed and random-effects models were used to calculate the summary risk estimates. We identified 26 observational studies of the JAK2 46/1 haplotype and risk of MPNs and SVT involving 8,561 cases and 7,434 participants. In the overall analysis, it was found that the JAK2 46/1 haplotype significantly elevated the risk of MPNs (rs10974944: C vs T: odds ratio (OR)?=?2.19, 95 % confidence interval (CI)?=?1.86–2.57, P?<?0.0001; CC vs TT: OR?=?4.63, 95 % CI?=?3.32–6.47, P?<?0.0001; CT vs TT: OR?=?2.49, 95 % CI?=?2.11–2.95, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.92, 95 % CI?=?2.51–3.39, P?<?0.0001; rs12343867: C vs T: OR?=?1.88, 95 % CI?=?1.59–2.22, P?<?0.0001; CC vs TT: OR?=?3.16, 95 %CI?=?2.14–4.65, P?<?0.0001; CT vs TT: OR?=?2.04, 95 % CI?=?1.51–2.74, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.25, 95 % CI?=?1.73–2.95, P?<?0.0001) and SVT (C vs T: OR?=?1.27, 95 % CI?=?1.06–1.52, P?=?0.011; CC vs TT: OR?=?2.33, 95 % CI?=?1.42–3.81, P?=?0.001; (CC?+?CT) vs TT: OR?=?1.25, 95 % CI?=?1.02–1.53, P?=?0.034). There was no evidence of a significant association between the rs12343867 and the risk of SVT in the genetic model (CT vs TT: OR?=?1.01, 95 % CI?=?0.80–1.29, P?=?0.906). This meta-analysis provides new evidence supporting the conclusion that the JAK2 46/1 haplotype enrichment is significantly associated with the development of MPNs and SVT in these patients.     

Lack of association between interleukin 23 receptor gene polymorphisms and rheumatoid arthritis susceptibility

The recent discovery of interleukin 23 (IL-23), its receptor, and the underlying signal transduction pathway has improved our understanding of cellular immunity. Several studies suggest that IL-23 is an essential promoter of chronic joint inflammation. In this report, we assess the possible association of interleukin 23 receptor (IL23R) polymorphisms and haplotypes with rheumatoid arthritis (RA). The study was conducted on 1,204 RA patients and 979 healthy controls. Seven polymorphisms were selected from previous IBD reports. The seven SNPs (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032 and rs1495965) were genotyped using the TaqMan assay. Comparison of RA and control subjects revealed no statistically significant differences in the distribution of the IL23R genotypes and haplotypes. Our results clearly indicate that IL23R gene polymorphisms do not play a significant role in susceptibility to RA in the Korean population. Accordingly, we conclude that IL23R gene polymorphisms cannot be applied as an effective genetic marker for RA susceptibility.     

The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis

Integrin αvβ3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin α_V (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Behçet’s disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6–3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3–3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1–7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p _ANOVA = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.     

白细胞介素-23R单核苷酸多态性与中国汉族人群强直性脊柱炎的关联分析

目的 研究白细胞介素(IL)-23R基因单核苷酸多态性(SNPs)与中国汉族人群强直性脊柱炎(AS)的相关性.方法 选取IL-23R基因SNPs位点rs11209026、rs1343151和rs11209032以及在物理距离上与它们相近的另外3个SNPs位点进行检测;采用聚合酶链反应(PCR)直接测序法进行基因分型;采用SPSS 13.0软件进行Hardy-Weinberg平衡、基因型和等位基因频率分析;采用SHEsis软件进行连锁不平衡和单倍型分析.结果 rs11209032位点的各基因型分布和rs6677188位点的各基因型与等位基因频率分布在病例组和对照组差异有统计学意义(P<0.01);rs6677188和rs11209032存在连锁不平衡关系(D'=0.925,r2=0.561);单倍型GAC和单倍型GTC在AS患者和健康对照者中的分布差异有统计学意义(p<0.01),其中单倍型GAC在AS患者高,而单倍型GTC在健康对照者高.结论 IL-23R基因单核苷酸多态性与中国汉族人群AS相关,IL-23R基因可能是AS的一个易感基因.     

Association between genetic variants in pre-miRNA and colorectal cancer risk in a Chinese population

Introduction

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA expression levels or processing and then contribute to the susceptibility of cancer development. We hypothesized that SNPs in pre-miRNAs may be associated with the risk of colorectal cancer (CRC).

Materials and methods

We genotyped four common polymorphisms (i.e., rs11614913, rs3746444, rs2910164, and rs2292832) in pre-miRNAs of 353 CRC patients and 540 healthy controls to investigate the association between the SNPs and the risk of CRC using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay.

Results

The rs11614913 CT, TT genotypes, and T allele were associated with an increased risk of CRC compared with the CC genotype and C allele (CT vs. CC: OR = 7.34, 95 % CI 3.76–14.34; TT vs. CC: OR = 13.66, 95 % CI 6.76–27.6; T vs. C: OR = 1.99, 95 % CI 1.63–2.42, respectively). Interestingly, using the rs2910164 GG genotype as a reference, the rs2910164 GC genotype was associated with an increased risk of CRC (OR = 1.49, 95 % CI 1.02–2.18), whereas the rs2910164 CC genotype was associated with a decreased risk of CRC (OR = 0.58, 95 % CI 0.37–0.93). When compared with the rs2910164G allele, rs2910164 C allele was associated with a reduced risk of CRC (OR = 0.80, 95 % CI 0.66–0.97, p = 0.02).

Conclusion

These findings suggest that rs11614913 and rs2910164 polymorphisms may be associated with the etiology of CRC.     

The PSCA polymorphisms derived from genome-wide association study are associated with risk of gastric cancer: a meta-analysis

Purpose

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-aa protein related to the cell-proliferation inhibition and/or cell-death induction activity. Many studies had reported the role of PSCA rs2294008 C?>?T and rs2976392 G?>?A polymorphisms on gastric cancer risk.

Methods

To investigate a more precise estimation of the relationships, we performed a meta-analysis on 9 case–control studies included 10,746 cases and 9,158 controls. Odds ratios (ORs) and 95?% confidence intervals (CIs) were used to assess the strength of the association.

Results

For PSCA rs2294008 C?>?T polymorphism, there was a significantly increased risk of gastric cancer in all genetic models (TT/TC vs. CC: OR?=?1.61, 95?% CI?=?1.35–1.91; TT vs. TC/CC: OR?=?1.33, 95?% CI?=?1.24–1.42). Similar results were also observed for PSCA rs2976392 G?>?A polymorphism (AA/AG vs. GG: OR?=?1.69, 95?% CI?=?1.24–2.31; AA vs. AG/GG: OR?=?1.36, 95?% CI?=?1.24–1.50). In the stratified analysis by ethnicity of rs2294008, an increased gastric cancer risk was found in both Asians (TT vs. TC/CC: OR?=?1.31, 95?% CI?=?1.22–1.42) and Europeans (TT/TC vs. CC: OR?=?1.42, 95?% CI?=?1.18–1.71). Furthermore, when stratified by clinicopathologic characteristics of tumor location and histology, a higher risk on non-cardia compared with cardia gastric cancer (TT vs. TC/CC: OR?=?1.43, 95?% CI?=?1.12–1.83) as same as diffused compared with intestinal gastric cancer (TT vs. TC/CC: OR?=?1.29, 95?% CI?=?1.13–1.49) was observed.

Conclusion

These findings supported that PSCA rs2294008 C?>?T and rs2976392 G?>?A polymorphisms may contribute to the susceptibility to gastric cancer, particular in non-cardia or diffused gastric cancer.     

IL-17 polymorphisms and asthma risk: a meta-analysis of 11 single nucleotide polymorphisms

Objective: There has been significant interest in the association between asthma and the polymorphisms of IL-17A and IL-17F for a period of time. This work aims to present a clearer relationship between asthma and the polymorphisms of IL-17A and IL-17F. Method: Searches were performed in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationship between polymorphisms of IL-17A and IL-17F and asthma. Results: Nine studies comprising 3650 asthmatics and 3370 controls were included in this meta-analysis for all single nucleotide polymorphisms (SNPs) (2–6 per SNP). Our study examined the polymorphisms of IL-17F rs1889570 (C/T) (CC versus TT: OR?=?0.55, 95%CI?=?0.41–0.75; CT versus TT: OR?=?0.54, 95%CI?=?0.40–0.72; CC/CT versus TT: OR?=?0.55, 95%CI?=?0.42–0.72; CC versus CT/TT, OR?=?1.83, 95%CI?=?1.39–2.41), IL-17A rs4711998(A/G) (AA/AG versus GG: OR?=?0.67, 95%CI?=?0.46–0.98), and IL-17A rs3819024(A/G) (AA versus GG: OR?=?1.77, 95%CI?=?1.39–2.25) and found they were significantly related to the risk of asthma. Conclusion: Our systematic review showed that IL-17F rs1889570(C/T), IL-17A rs4711998(A/G) and IL-17A rs3819024(A/G) may be potential risk factors for asthma susceptibility.     

TLR9 polymorphisms and systemic lupus erythematosus risk: an update meta-analysis study

It has been reported that the Toll-like receptor 9 (TLR9) gene polymorphisms may be associated with systemic lupus erythematosus (SLE) risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was performed to assess the precise association between TLR9 polymorphisms and SLE susceptibility. We performed a systematic search in PubMed, Embase (Ovid), China National Knowledge Internet, and Wanfang databases up to July 15, 2015. Odds ratio (OR) and 95 % confidence interval (CI) were used to pool the effect size. Statistical analyses were performed with STATA 11.0 software. In total, 21 studies from nineteen articles with 10,273 subjects were included in this meta-analysis. The overall results suggested that there was a statistically significant association between TLR9 rs187084 polymorphism and SLE risk observed in recessive model (TT vs. TC + CC: OR 1.17, 95 % CI 1.05–1.30, P = 0.005), codominant model (TT vs. CC: OR 1.22, 95 % CI 1.03–1.43, P = 0.019), and allele model (T vs. C: OR 1.15, 95 % CI 1.02–1.30, P = 0.020) in Asians. However, we found that there may be no significant association between the other three TLR9 polymorphisms and SLE risk in either Asians or non-Asians. In conclusion, the meta-analysis results suggested that TLR9 rs187084 polymorphism may increase the risk of SLE in Asians. However, no significant association between TLR9 SNPs (rs352139, rs352140, and rs5743836) and SLE risk was identified.     

The Drosha rs10719 T>C polymorphism is associated with preeclampsia susceptibility

Purpose: Drosha is a member of the micro RNA (miRNA) processing machinery that affects miRNA processing. Single-nucleotide polymorphisms (SNPs) in the Drosha gene might affect microRNA processing and the expression of various genes. The aim of this study is to investigate the association between SNPs in the Drosha gene and preeclampsia (PE) in the southeast of Iran. Methods: Genotyping of Drosha rs10719 and rs6877842 was performed using blood samples from 219 PE women and 205 healthy control subjects by a polymerase chain reaction-restriction fragment length polymorphism method. Results: The Drosha rs10719TC genotype was significantly associated with 1.6-fold higher risk of PE (odds ratio (OR, 1.6 [95% CI, 1.1–2.4], P = 0.026). In addition, the frequency of the Drosha rs10719CC genotype was significantly higher in PE women and was associated with threefold higher risk of PE (OR 3 [95% CI 1.4–6.3], P = 0.004). There was no association between the Drosha rs6877842 polymorphism and PE susceptibility. The CC–GG combined genotype was associated with 3.4-fold higher risk of PE (OR 3.4 [95% CI 1.4–8.1], P = 0.007). The haplotype-based association analysis showed higher frequency of C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms with the increased risk of PE 1.5-fold (OR 1.5 [95% CI 1.1 – 2], P = 0.01). Conclusions: The Drosha rs10719TC and CC genotypes were associated with PE risk. The CC–GG combined genotype and C–G haplotype of Drosha rs10719 and rs6877842 polymorphisms may increase PE susceptibility.