Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

Abstract

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR = 0.81, P = 0.117; for CC vs. TT: OR = 0.71, P = 0.158; for CT vs. TT: OR = 0.86, P = 0.085; for CC + CT vs. TT: OR = 0.78, P = 0.093; for CC vs. CT + TT: OR = 0.81, P = 0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR = 1.11, P = 0.095; for GG vs. AA: OR = 1.32, P = 0.238; for GA vs. AA: OR = 1.17, P = 0.084; for GG + GA vs. AA: OR = 1.17, P = 0.073; for GG vs. GA + AA: OR = 1.17, P = 0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR = 1.02, P = 0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

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 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.     

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086–7.090, p?=?0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727–6.661, p?=?0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379–1.472, p?=?0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544–1.956, p?=?0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.     

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.     

Toll-Like Receptor (TLR)-9 rs352140 Polymorphism is an Immunopathology Protective Factor in Parkinson's Disease in the Northern Iranian Population

Background: Neuroinflammation and immunopathology in Parkinson's disease (PD) are believed to be associated with genetic and environmental factors. Objective: We conducted the current study to evaluate the Toll-like receptors (TLR4 and TLR9) genes polymorphism in patients with Parkinson's disease in northern Iran. Methods: We extracted DNA from peripheral blood samples of 100 sporadic cases of Parkinson's disease and 100 healthy-matched controls with the mean age of 69.98 and 71.94 years, respectively. Subsequently, single-nucleotide polymorphisms (SNPs) of TLR4 and TLR9 were genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results were confirmed employing Sanger sequencing. For the analysis of our data, we used SNPStats and SPSS 22 software. Results: Our findings indicated that the allele distribution for rs352140 of TLR9 gene was significantly different in the PD group compared with the healthy controls (p=0.02). Moreover, rs352140 T allele was observed to be correlated with PD reduced risk (TT + TC vs. CC). The dominant rs352140 model was approved as the most acceptable inheritance model for fitting the data (OR 0.41, 95% CI 0.23-0.75, p=0.0031). Additionally, haplotype analysis revealed a significant correlation between TLR9 polymorphisms and Parkinson's disease. Conclusion: The results of this study indicated that rs352140T of TLR9 gene was a protective factor in Parkinson's disease. Furthermore, this SNP could be regarded as a prognostic factor. However, this conclusion should be confirmed by further investigations.     

Association of toll-like receptor 9 gene polymorphism in Chinese patients with systemic lupus erythematosus in Taiwan

The purpose of this study was to determine whether toll-like receptor 9 (TLR9) gene polymorphisms were markers of susceptibility to or severity of systemic lupus erythematosus (SLE) in Taiwanese patients. The study included 211 healthy individuals and 167 Chinese patients with SLE. Polymorphisms of TLR9 [rs2066807 and rs187084 (?1486 T/C)] were typed from genomic DNA. The genotypes, allelic frequencies, and carriage rates were compared between patients with SLE and control subjects. The relationship between allelic frequencies and clinical manifestations of 167 patients with SLE was evaluated. There was no statistically significant difference in TLR9 (rs2066807) gene polymorphism, allelic frequency, and carriage rate between the SLE and control groups. However, for the genotype of TLR9 ?1486 T/C (rs187084) polymorphism, there was a statistically significant difference between the SLE and the control groups (P?<?0.001, χ²?=?15.9). Moreover, there was a significant association between the two groups in allelic frequency and carriage rate of the T allele (P?<?0.001, χ²?=?18.5 and P?<?0.01, χ²?=?8.06, respectively). We did not detect any association between the TLR9 genotype and the clinical or laboratory profiles in patients with SLE. The results suggest that the TLR9 ?1486 T/C (rs187084), but not TLR9 (rs2066807), polymorphism is related to SLE in Taiwanese patients.     

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 between PDE4D rs966221 polymorphism and risk of ischemic stroke: a systematic review and meta-analysis

PDE4D polymorphism (SNP83/rs966221) was reported to be associated with the susceptibility to ischemic stroke (IS), however, the results were inconclusive. An electronic search of Embase, PubMed, CNKI and Wan Fang Date was performed to identify relevant studies published throughout April 2017. A total of 26 studies were enrolled in the analysis. No significant association between the rs9662221 polymorphism and IS was observed in the overall analysis. Nevertheless, in the subgroup analysis, our results showed a significant association between the SNP83 polymorphism and IS in CC+ CT vs. TT (OR?=?1.19, 95% CI: 1.02–1.38), CT vs.TT (OR?=?1.14, 95% CI: 1.01–1.29) and C vs. T (OR?=?1.25, 95% CI: 1.06–1.48) in Asian population. But we did not found any association in CC vs. CT?+?TT (OR?=?1.2, 95% CI: 0.9–1.61) and CC vs. TT (OR?=?1.26, 95% CI: 0.91–1.75) in the Asian populations. Meantime, no significant correlations were observed under the five genetic model in Caucasian population (p?>?0.05). In conclusion, our meta-analysis demonstrated that the SNP83 polymorphism in the PDE4D gene might contribute to IS susceptibility especially in Asian populations. Whereas the relationship of the polymorphism to the disease in Caucasian population was still in controversial. In future, additional well designed studies with larger sample sizes are still required to further elucidate this association.     

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.     

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.     

Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients

Abnormal innate immune responses toward luminal bacteria play an important role in the pathogenesis of inflammatory bowel disease.It has been demonstrated that bacteria having CpG DNA ameliorate experimental colitis in mice,and Toll-like receptor 9 (TLR9) signaling mediates the anti-inflammatory effects in mouse colonic inflammation.A gene variation in NOD2/CARD15 has been reported in Crohn’s disease (CD) patients in Western countries,but this variation has not been identified in Japanese CD patients.Therefore,we hypothesized that TLR9 is a key factor in the development of ulcerative colitis (UC),and we investigated gene mutations and polymorphisms of TLR9 in Japanese UC patients.Three single nucleotide polymorphisms (SNPs) in TLR9 were identified in healthy controls,and were assessed in 48 UC patients and 47 healthy controls.Control subjects were matched for age,sex and date of blood sampling from among a subgroup of participants.We found that TLR9-1486CC,1174GG and 2848AA increase the risk of UC [odds ratio (OR) 2.64,95% confidence interval (95% CI):1.73-6.53,P=0.042],and TLR9-1486TT,1174AA and 2848GG decrease the risk of UC (OR 0.30,95% CI:0.10-0.94,P=0.039),although there were no correlations between SNPs and disease phenotype or TLR9 mRNA expression.These findings suggest that TLR9 polymorphisms are associated with increased susceptibility to UC.     

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.     

A polymorphism near osteoprotegerin gene confer risk of obesity in Uyghurs

To investigate the association of single nucleotide polymorphism (SNP) rs4355801 near osteoprotegerin (OPG) gene and rs3736228 in low-density lipoprotein receptor-related protein 5 (LRP5) gene with metabolic phenotypes [body mass index (BMI), waist-hip ratio, glucose, total cholesterol (CHO), and triglyceride], we carried out a population-based association study in Uyghur population living in Xinjiang Uyghur Autonomous Region of China. We observed a significant higher level of BMI in AG/AA carriers than in GG carriers (P?=?0.022) for rs4355801. Subjects with the AG/GG genotype significantly increased the risk of BMI related obesity than subjects with the AA genotype, with an odds ratio of 1.31 (95% CI 1.09-1.56, P?=?0.005). The association remained significant after controlling for covariates of age and gender. In addition, we observed a significant higher level of CHO in CT/TT carriers than in CC carriers (P?=?0.021) for rs3736228. Our observations provide the first evidence that rs4355801 near OPG gene may confer susceptibility to obesity. In addition, SNP rs3736228 in LPR5 gene may affects the level of CHO in Uyghur population.     

TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12-2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population.     

Ⅰ型血管紧张素Ⅱ受体相关蛋白基因多态性与高血压的相关性研究

目的探讨Ⅰ型血管紧张素Ⅱ受体相关蛋白(AT1 receptor-associated protein,ARAP1)基因的常见多态rs2787594,rs11795066,rs13298677和rs4837129与高血压之间的关联关系。方法选择503例高血压病例和490例年龄、性别相匹配的健康对照。所有个体均为中国北方汉族人。采用多聚酶链式反应一限制性片段长度多态性(PCR-RFLP)方法进行基因型鉴定。结果校正协变量前后,所有SNPs均与高血压无关联。单体型分析也没有发现与高血压关联的单体型。应用线性回归模型校正年龄和性别的作用,比较不同基因型个体的体重指数(BMI)、血糖和血脂水平的差异。rs2787594多态CC纯合子与升高的血糖水平显著关联(CC/TT+TC,6.09+0.24vs.5.54+0.08mmol/L,P=0.0296)。在显性模型中,rs11795066 A等位基因显著升高了个体的BMI水平(GA+AA/GG,24.81±0.29vs.24.07±0.19kg/m2,P=0.0331)。rs13298677多态G等位基因与较低的BMI水平(GG/GA+AA,22.84±0.74vs.24.37±0.16kg/m2,P=0.0438)以及TG水平(GG+GA/AA,1.34±0.06vs.1.50±0.05mmol/L,P=0.0413)显著关联。结论 ARAP1基因4个SNPs与高血压无显著关联,但与对照个体的血脂、血糖和BMI关联,该基因变异可能影响了我国人群血脂、血糖的代谢。     

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.     

Glucocorticoid Receptor Gene Polymorphisms and Glucocorticoid Resistance in Inflammatory Bowel Disease: A Meta-Analysis

Background

Studies investigating the associations between glucocorticoid receptor gene polymorphisms and glucocorticoid resistance in inflammatory bowel disease report conflicting results.

Aims

We conducted a meta-analysis to assess the possible association between the three most commonly investigated glucocorticoid receptor gene (ER22/23EK, N363S, and BclI) polymorphisms and glucocorticoid resistance in inflammatory bowel disease.

Methods

Articles evaluating the effect of ER22/23EK, N363S, and BclI gene polymorphism on glucocorticoid resistance in inflammatory bowel disease were identified from 1950 to February 2012. After extraction of relevant data, meta-analyses were performed to assess the association between glucocorticoid receptor gene polymorphisms and glucocorticoid resistance in inflammatory bowel disease.

Results

A total of five eligible studies with 942 cases were included. Our analysis showed that ER22/23EK polymorphisms were not associated with glucocorticoid resistance in inflammatory bowel disease [GG versus GA?+?AA: odds ratio (OR)?=?0.58, 95?% confidence interval (CI) 0.16?C2.08]. In N363S polymorphisms, AG?+?GG allele showed no significant effect on glucocorticoid resistance in inflammatory bowel disease compared with AA allele (OR?=?1.19, 95?% CI 0.33?C4.30). In BclI polymorphisms, there was also no association of CG?+?GG allele with glucocorticoid resistance (CC versus CG?+?GG: OR?=?1.22, 95?% CI 0.70?C2.13). For Crohn??s disease (CD) and ulcerative colitis (UC), no statistically significant associations between these three single-nucleotide polymorphisms (SNPs) and glucocorticoid resistance were found. The shape of the funnel plot did not detect publication bias.

Conclusions

The current meta-analysis found no evidence that glucocorticoid receptor gene polymorphisms (ER22/23EK, N363S, and BclI) are associated with glucocorticoid resistance in inflammatory bowel disease treatment. However, this meta-analysis is underpowered for relatively large effect sizes in some SNPs. More well-designed cohort studies should be conducted to fully characterize such an association.     

Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.     

Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis

We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) and AA?+?AG vs. GG (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR?=?1.383, 95 % CI 1.142–1.676, P?=?0.022) and AA vs. AG?+?GG (OR?=?1.575, 95 % CI 1.361–1.823, P?<?0.001) in European patients with Crohn’s disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG?+?GG (OR?=?0.713, 95 % CI 0.545–0.933, P?=?0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.