Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

Associations between interleukin-10 polymorphisms and susceptibility to psoriasis: a meta-analysis

Objective

The aim of this study was to determine whether three specific interleukin-10 (IL-10) polymorphisms confer susceptibility to psoriasis.

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -592 C/A polymorphisms and haplotypes of the IL-10-1082 G/A, -592 C/A, -819 C/T polymorphisms and psoriasis.

Results

A total of eight studies involving 1,018 psoriasis patients and 1,186 controls were considered in the meta-analysis. No association was found between psoriasis and the IL-10-1082 G allele in all study subjects [odds ratio (OR)?=?1.098, 95?% confidence interval (CI)?=?0.923?1.306, p?=?0.291] or between this allele and psoriasis in Europeans (OR?=?0.990, 95?% CI?=?0.809?1.214, p?=?0.925), but a significant association was found in Asians (OR?=?1.785, 95?% CI?=?1.144?2.76, p?=?0.011). Three polymorphisms at the promoter region of IL-10 (-1082 G/A, -819 C/T, -592 C/A) are known to be in complete linkage disequilibrium, but no association was found between the haplotype and psoriasis.

Conclusions

This meta-analysis shows that the IL-10-1082 G/A polymorphism confers susceptibility to psoriasis in Asians, and suggests that the IL-10 promoter -1082 polymorphism has an ethnicity-specific effect.     

Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis

Objective

The aim of this study was to determine whether phox homology domain containing serine/threonine kinase (PXK) and tyrosine kinase 2 (TYK2) confer susceptibility to systemic lupus erythematosus (SLE).

Materials and methods

The authors conducted meta-analyses on associations between SLE susceptibility and the rs6445975 polymorphism of PXK and the rs2304256, rs12720270, rs280519, and rs1272036 polymorphisms of TYK2.

Results

A total of 13 separate comparisons studies were included in this meta-analysis. Meta-analysis identified an association between SLE and the 2 allele of the rs6445975 polymorphism in the overall population [odds ratio (OR)?=?1.151, 95?% confidence interval (CI)?=?1.086–1.291, P?=?1.8E?06]. Stratification by ethnicity identified a significant association between this polymorphism and SLE in Europeans (OR?=?1.198, 95?% CI?=?1.118–1.285, P?=?3.4E?07), but not in Asians. Meta-analysis identified a significant negative association between SLE and the 2 allele of the rs2304256 polymorphism in the overall population (OR?=?0.808, 95?% CI?=?0.659–0.990, P?=?0.040), and a significant negative association was found in Europeans, but not in Asians.

Conclusions

This meta-analysis shows that the rs6445975 polymorphism of PXK and the rs2304256 polymorphism of TYK2 are associated with the development of SLE in Europeans.     

IL-10RA基因多态性与SLE发病关系的临床研究

目的:研究中国北方人群白细胞介素10受体A(IL-10RA)基因多态性分布情况,探讨IL-10RA基因变异与系统性红斑狼疮发病的相关性.方法:利用基因测序、PCR扩增及单链构象多态性(Single-strand Conformation Polymorphism,SSCP)电泳技术,对IL-10RA基因多态性进行筛选及分析,比较系统性红斑狼疮病例组与健康对照组中基因型的分布频率.结果:在IL-10RA第5内含子处存在3种有意义单核苷酸多态性(SNP),即T/T型、C/C型、C/T型.其中T/T型和C/T型在病例组中的出现频率明显增加.结论:IL-10RA内含子5具有多态性并与系统性红斑狼疮的发病相关.     

Associations between TNFSF4 and TRAF1-C5 gene polymorphisms and systemic lupus erythematosus: A meta-analysis

Objective

The aim of this study was to determine whether tumor necrosis factor superfamily 4 (TNFSF4) and TNF receptor-associated factor 1-complement 5 (TRAF1-C5) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

The authors conducted meta-analyses on associations between polymorphisms of the TNFSF4 (rs2205960, rs1234315, rs10489265) and TRAF1-C5 (rs10818488, rs3761847) genes and SLE susceptibility, using fixed and random effects models.

Results

A total of 21 comparative studies were included in this meta-analysis; meta-analysis showed an association between the minor allele of rs2205960 of TNFSF4 and SLE in all study subjects (odds ratio [OR] = 1.356, 95% confidence interval [CI] = 1.275–1.442, p < 1.0 × 10⁻⁹). Meta-analysis revealed an association between the minor alleles of rs1234315 and rs10489265 of TNFSF4 and SLE in Asians (OR = 1.366, 95% CI = 1.295–1.440, p < 1.0 × 10⁻⁹; OR = 1.463, 95% CI = 1.208–1.771, p = 9.7 × 10⁻⁵). The minor allele of rs10818488 of TRAF1-C5 was found to be significantly associated with SLE in Europeans (OR = 1.210, 95% CI = 1.115–1.313, p = 5.0 × 10⁻⁶). The association p-values remained significant after multiple corrections.

Conclusions

This meta-analysis confirms that TNFSF4 polymorphisms are associated with susceptibility to SLE in Asians and Europeans. An association was found between the rs10818488 polymorphism of TRAF1-C5 and susceptibility to SLE in Europeans.     

Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus

Several lines of evidence suggest interleukin-10 gene (IL-10) is a candidate gene in susceptibility to systemic lupus erythematosus (SLE). We investigated the association of IL-10 promoter single-nucleotide polymorphisms (SNPs) (-3575T/A, -2849G/A, -2763C/A, -1082A/G, -819T/C and -592A/C) and microsatellites (IL10.R, IL10.G) with SLE in 554 Hong Kong Chinese patients and 708 ethnically matched controls. Six haplotypes (hts) were identified from the SNPs. The genotype distribution of the ht1 (T-C-A-T-A), which is associated with low IL-10 production, was different in patients and controls (P=0.009). The homozygous genotype of non-ht1 was significantly increased in patients (P=0.009, odds ratio (OR)=1.80, 95% CI: 1.15-2.82). The frequency of IL10.G4 of IL10.G was also significantly increased in patients (P=0.017, OR=2.53, 95% CI: 1.18-5.40). We found that the homozygous non-ht1 combined with short allele (CA repeat number < or =21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27-13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26-7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62-1.78, P=0.848). The frequency of non-ht1 was significantly increased in patients with serositis (P<0.0001, OR=2.42, 95% CI: 1.55-3.80). In conclusion, the high expression promoter genotype is associated with SLE in Chinese.     

Associations between <Emphasis Type="Italic">eNOS</Emphasis> polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis

Objective  

To determine whether endothelial nitric oxide synthase (eNOS) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).     

Associations between interleukin-23R and interleukin-12B polymorphisms and psoriasis susceptibility: a meta-analysis

Objective: The aim of this study was to determine whether interleukin (IL)-23?R and IL-12B polymorphisms confer susceptibility to psoriasis.

Methods: The authors conducted a meta-analysis on associations between the IL-23?R and IL-12B polymorphisms and psoriasis susceptibility.

Results: A total of 14 comparison studies were included in this meta-analysis. The meta-analysis identified a significant association between psoriasis and 2 alleles of the rs11209026 and rs7530511 polymorphisms in Europeans (odds ratio [OR]?=?0.624, 95% confidence interval [CI]?=?0.565–0.697, p?<?1.0?×?10^?8; OR?=?0.804, 95% CI?=?0.743–0.869, p?=?3.0?×?10^?7, respectively). Meta-analysis of IL-12B showed a significant association between the 2 alleles of the rs6887695 and rs3212227 polymorphisms and the risk of developing psoriasis (OR?=?0.710, 95% CI?=?0.673–0.749, p?<?1.0?×?10^?8; OR?=?0.684, 95% CI?=?0.639–0.731, p?<?1.0?×?10^?8, respectively). Stratification by ethnicity identified an association between the rs6887695 and rs3212227 polymorphisms and psoriasis in Europeans.

Conclusions: This meta-analysis showed that the IL-23?R (rs11209026 and rs7530511) polymorphisms are associated with psoriasis risk in Europeans and that the IL-12B (rs6887695 and rs3212227) polymorphisms are associated with susceptibility to psoriasis in Europeans.     

Association between complement gene polymorphisms and systemic lupus erythematosus: a systematic review and meta-analysis

Clinical and Experimental Medicine - Complement dysfunction results in impaired ability in clearing apoptotic cell debris that may stimulate autoantibody production in systemic lupus erythematosus...     

Association between polymorphisms at the human IL-10 locus and systemic lupus erythematosus

Recent studies have shown elevated IL-10 levels in several rheumatic autoimmune diseases, and particularly in systemic lupus erythematosus (SLE). Such changes may have a genetic basis. We studied two novel polymorphic dinucleotide repeats in the IL-10 promoter region (IL 10.G and IL 10.R) in order to investigate their possible significance in association with this condition in a group of 56 Caucasian SLE patients compared with 102 ethnically matched controls. The results show that there is an allelic imbalance between SLE patients and controls at the IL 10.G microsatellite; this observation is supported by a significant difference in genotype distribution. The nature of autoantibody production and the presence or absence of renal involvement also appeared to be associated with certain IL 10.G microsatellite alleles, although the small size of individual clinical sub-groupings may have influenced this result. No association with the IL 10.R microsatellite was observed. Overall, the differences observed at the IL 10.G microsatellite between SLE patients and controls suggest that the IL-10 locus contributes to the genetic background important for the development of this disease. Although the moderate sample size described in this study requires that the results be interpreted carefully, they provide an interesting and useful framework for future study.     

CTLA-4启动子区基因多态性与系统性红斑狼疮关系的meta分析

目的:评价CTLA-4基因多态性与系统性红斑狼疮(SLE)易感性之间的相关性.方法:检索PubMed、Web of Knowledge、Embase、万方学术期刊全文数据库、中国期刊全文数据库和中国生物医学数据库,检索CTLA-4多态性与SLE易感性相关的文献,末次检索时间为2012-05-20.使用Meta分析方法对数据进行分析.结果:共纳入12篇文献,共涉及CTLA-4启动子区域3个多态位点:-1722、-166及-318位点,全人群研究结果显示在CTLA-4基因-1722T/C多态性(显性模型下:OR=2.570,95％CI=1.845-3.581,P＜0.01)及-318T/C多态性(隐性模型:OR =0.044,95％CI=0.020-0.094,P＜0.01)与SLE存在统计学上的相关性,人群分层后亚裔人群中-1722T/C及-318T/C多态性与SLE的此种相关性仍存在,但欧裔及非裔人群的CTLA-4启动区所有研究位点均未发现与SLE有关.结论:CTLA-4基因1722T/C及-318T/C多态性可能与SLE人群易感性有关,特别是亚裔人群.     

Associations between TNFSF15 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: A meta-analysis

Abstract

Aims: Several polymorphisms have been identified in TNFSF15, while their roles in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk. Method: Databases were searched until 31 January 2014 for eligible studies on TNFSF15 polymorphisms. Data were extracted, and pooled odd ratios (ORs) as well as 95% confidence intervals (95% CIs) were calculated. Results: Fifteen studies with 8903 CD patients, 4687 UC patients and 12?606 controls were included. Except for rs4263839 polymorphism, significant associations were found between the rest six TNFSF15 polymorphisms and CD risk (rs3810936: OR?=?2.10, 95% CI, 1.47–3.00; rs6478108: OR?=?2.19, 95% CI, 1.53–3.13; rs4979462: OR?=?1.89, 95% CI, 1.42–2.52; rs6478109: OR?=?2.00, 95% CI, 1.39–2.88; rs7848647: OR?=?1.54, 95% CI, 1.15–2.06; rs7869487: OR?=?1.51, 95% CI, 1.06–2.17). And we found rs3810936, rs6478108 and rs6478109 polymorphism were significantly associated with UC risk (rs3810936: OR?=?1.19, 95% CI, 1.06–1.34; rs6478108: OR?=?1.16, 95% CI, 1.06–1.26; rs6478109: OR?=?1.16, 95% CI, 1.03–1.32). According to the subgroup analysis by ethnicity, except for rs4263839 in Caucasian and rs4979462 in Asian, all the rest investigated TNFSF15 polymorphisms were associated with CD risk and rs3810936 and rs7848647 polymorphism in Asian as well as rs6478108 polymorphism in Caucasian were associated with UC risk. Conclusion: This meta-analysis indicated that most of the seven TNFSF15 polymorphisms (except for rs4263839) were risk factors contributed to CD and UC susceptibility. The differences in ethnicity did not influence the risk obviously.     

The association between BANK1 and TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis

The past decade has witnessed hundreds of reports declaring or not being able to replicable genetic association with systemic lupus erythematosus (SLE) susceptibility. BANK1 is a gene that encodes a B‐cell‐specific scaffold protein and its activation can affect B‐cell‐receptor‐induced calcium mobilization from intracellular calcium stores. TNFAIP3 encodes the ubiquitin‐modifying enzyme, also known as A20, which is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa‐B (NFKB) activity and tumour necrosis factor (TNF)‐mediated programmed cell death. The association of BANK1 and TNFAIP3 polymorphism with SLE has been reported in several studies. The aim of this study was to assess whether combined evidence shows the association between BANK1 and TNFAIP3 polymorphism and SLE. We report the results of a meta‐analysis of genome‐wide association scans and replication in independent sets for BANK1 and TNFAIP3 polymorphism and SLE that includes 12 416 subjects with SLE and 19 113 control subjects. Meta‐odds ratios (ORs) and 95% confidence intervals (CIs) based on random effects models. Both of BANK1 and TNFAIP3 harbour several controversial single nucleotide polymorphisms (SNPs). We selected and identified three SNPs of BANK1 associated with SLE (rs17266594, P = 1.949e‐10; OR = 1.380; 95% CI: 1.250–1.525; rs10516487, P = 2.642e‐13; OR = 1.317; 95% CI: 1.223–1.417; rs3733197, P = 3.452e‐06; OR = 1.193; 95% CI: 1.107–1.286); one SNP of TNFAIP3 associated with SLE (rs2230926, P = 1.502e‐12; OR = 1.826; 95% CI: 1.545–2.157). This meta‐analysis demonstrates a significant association between BANK1 and TNFAIP3 gene polymorphism and SLE in multiple ethnic populations. These findings reinforce the value of large sample series for discovery and follow‐up of genetic variants contributing to the aetiology of SLE.     

PDCD1 single nucleotide genes polymorphisms confer susceptibility to juvenile-onset systemic lupus erythematosus

Abstract

Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease in which both the genetic and environmental factors seem to be involved in the etiopathogenesis of the disease. The aim of this study was to evaluate the association of programmed cell death 1 (PDCD1, also called PD-1) gene polymorphisms with JSLE susceptibility in Iranian population. In this case-control association study, three PDCD1 SNPs, including PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T were genotyped in 50 Iranian patients with JSLE and 202 healthy unrelated controls, using PCR-RFLP method. The PD-1.1 A allele was found to be more frequent in the case group compared with controls (6% vs. 1.5%, p?=?0.024). Moreover, the GG genotype was less frequent in cases than in controls (88% vs. 97%, p?=?0.021). The other PDCD1 SNPs did not show association. At the haplotypic level, no significant differences was recognized between the two groups of case and control neither for the GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C) nor for the GGC haplotype (PD-1.1 G, PD-1.3 G, PD-1.9 C). Our findings support the influence of the PD1.1 A SNP on the development of JSLE in Iranian population.     

Associations between interleukin 17A and 17F polymorphisms and asthma susceptibility: A meta-analysis

Owing to their role in inflammatory reactions and immunological responses as well as their chromosomal location, interleukin (IL) 17A and 17F are regarded as candidate causal genes associated with asthma. The aim of this study was to determine whether IL17 polymorphisms are associated with susceptibility to asthma. We used the PubMed/Medline and Embase databases to search for studies reporting IL17 polymorphisms in patients with asthma and healthy controls. Meta-analyses were conducted to determine the associations between IL17A rs8193036 (−737C/T), rs2275913 (−197G/A), rs3819024 (A/G), rs3748067 (C/T), and rs4711998 (A/G) and IL17F rs763780 (7488A/G), rs2397084 (T/C), rs1889570 (C/T), rs11465553 (G/A), and rs1266828 (T/C) polymorphisms and asthma susceptibility. A total of 20 studies were included in this meta-analysis. Our results revealed the IL17A rs8193036 CC genotype was associated with asthma susceptibility (odds ratio [OR] = 1.490, 95% confidence interval [CI] = 1.027–2.161, p = .036). However, stratification by ethnicity indicated no association between this polymorphism and asthma in European and Asian subjects. Furthermore, no association was found between this polymorphism and asthma using the allele contrast, dominant or homozygous contrast models. No evidence of an association was found between any of the other IL17A and IL17F polymorphisms and asthma susceptibility in this meta-analysis. This meta-analysis showed that, among the studied polymorphisms, only the CC genotype of IL17A rs8193036 is associated with asthma susceptibility.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

Interferon-gamma polymorphisms in systemic lupus erythematosus

Interferon-gamma is a cytokine which is believed to play a role in both the susceptibility and pathogenesis of lupus. To determine whether genetic variants might influence the development of this polygenic autoimmune disease, we analyzed the gene frequency of eight different alleles in controls and patients with SLE. Ninety-nine controls and 136 patients with systemic lupus erythematosus were genotyped for a CA repeat in the first intron of the interferon-gamma gene. There were no statistically significant differences in the allele frequencies between patients and controls suggesting that these polymorphic variants do not influence susceptibility. We then examined whether any of these alleles were associated with specific clinical manifestations. Allele 1 was associated with gastrointestinal lupus while allele 6 was associated with more severe lupus. Allele 2 appeared to be protective for arthritis. This suggests that genetic variation in interferon-gamma expression might influence the disease course.