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Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124–0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127–0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have focused on the special roles of NADPH-oxidase in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in a Chinese population. We performed this study to examine the association of NCF2, NCF4, and CYBA gene polymorphisms with RA susceptibility in a Chinese population.Methods: Six single nucleotide polymorphisms (SNPs) (NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, and rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. Improved multiple ligase detection reaction (iMLDR) was used for genotyping.Results: We observed that NCF4 rs4821544 CT genotype and C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT: P = 0.043; C vs. T: P = 0.031), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC: P = 0.031). Our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC: P = 0.033). Moreover, the rs729749 CT genotype frequency was also significantly decreased in RA patients in males (CT vs. CC: P = 0.024). No significant association between NCF2 and CYBA gene polymorphisms and RA susceptibility was observed. There were significant associations between rs4821544 TT genotype and T allele frequencies and anti-CCP in male RA patients.Conclusions: In summary, NCF4 rs4821544 and rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 and CYBA gene polymorphisms were not associated with RA susceptibility. [ABSTRACT FROM AUTHOR]

Purpose: To explore the association of adiponectin (AD) and adiponectin receptor (ADR) gene single-nucleotide polymorphisms (SNPs) with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population.Study Design: Five AD SNPs (rs266729, rs2241766, rs1063537, rs2082940 and rs1063539) and two ADR SNPs (rs7539542 and rs12342) were genotyped in a cohort of 617 patients with RA and 639 healthy controls. Seven SNPs were genotyped using TaqMan genotyping assays on the Fluidigm 192.24 system. The concentration of AD in plasma was examined by ELISA.Results: Patients with RA showed a considerably lower plasma level of AD than healthy controls (p=0.002). No significant differences were observed for the distribution of allele and genotype frequencies of rs266729, rs2241766, rs2082940, rs1063539, rs7539542 and rs12342 SNPs between patients with RA and controls. The genotype effects of recessive and dominant models were also analysed, but no marked evidence for association was found. However, further analysis in female patients with RA showed that the frequency of the AD gene rs1063539 GG genotype was nominally significantly higher in patients who were anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (p=0.040). No significant differences in serum AD level were observed in patients with RA with different genotypes.Conclusions: rs266729, rs2241766, rs2082940 and rs1063539 in the AD gene and rs7539542 and rs12342 in the ADR gene are possibly not associated with genetic susceptibility to RA, but the AD gene rs1063539 locus was possibly associated with anti-CCP in RA female patients. [ABSTRACT FROM AUTHOR]

In a previous study, we have reported an increased plasma midkine (MK) and pleiotrophin (PTN) concentrations in patients with systemic lupus erythematosus (SLE) and the increase in MK and PTN associated with inflammatory cytokines interleukin (IL)-17 level and some clinical manifestations, suggesting the underlying association of MK and PTN with SLE. This study was conducted to investigate the association between common single-nucleotide polymorphisms (SNPs) in the MK and PTN gene and SLE susceptibility. A total of 989 subjects (496 SLE patients and 493 healthy controls) were included and genotyped for three MK SNPs and seven PTN SNPs in using improved multiple ligase detection reaction (iMLDR). Results have demonstrated no significant differences for genotype and allele frequencies in all 10 SNPs between SLE patients and healthy controls. Case-only analysis in SLE revealed that, in MK gene, the genotype frequency of AA/AG (rs35324223) was significantly lower in patients with photosensitivity than those without; the allele frequency of A/G (rs20542) was significantly higher in patients without serositis. In PTN gene, the A/G allele frequency (rs322236), C/T allele frequency, and TT/CT genotype frequency (rs6970141) showed significantly increased results in patients with immunological disorder compared to those without. Furthermore, no significant differences in plasma MK and PTN concentrations with its SNPs genotypes were found. MK and PTN SNPs showed no associations with SLE genetic susceptibility, but it may be associated with the course of this disease; further studies are needed to focus on the mechanism of MK and PTN genes in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are increasingly recognized to play important roles in multiple autoimmune diseases. This study aimed to evaluate the association of four lncRNAs (ANRIL, lnc-DC, MALAT1, ZFAS1) genes single nucleotide polymorphisms (SNPs) with susceptibility to rheumatoid arthritis (RA) patients, as well as their expression levels. Seventeen SNPs of the four lncRNAs were genotyped in a cohort of 660 RA patients and 710 controls using improved multiple ligase detection reaction (iMLDR). The lncRNAs expressions in peripheral blood mononuclear cells (PBMCs) from 120 RA patients and 120 controls were detected by qRT-PCR. No significant differences were found for the allele and genotype frequencies distribution of ANRIL SNPs (rs1412830, rs944796, rs61271866, rs2518723, rs3217992) , lnc-DC SNPs (rs7217280, rs10515177) , MALAT1 SNPs (rs619586, rs4102217, rs591291, rs11227209, rs35138901), ZFAS1 SNPs (rs237742, rs73116127, rs6125607, rs6125608) between RA patients and normal controls (all P > 0.05). The genotype effects of dominant and recessive models were also evaluated, but no significant association was found. In addition, our results demonstrated that the rs944796 G allele, rs2518723 T allele, rs3217992 T allele frequencies were significantly associated with anti-CCP in RA patients (all P < 0.05). The haplotype CGTA frequency for ZFAS1 was significantly higher in RA patients (P = 0.036). Compared with normal controls, the expression levels of ANRIL, lnc-DC, MALAT1, ZFAS1 in PBMCs were significantly reduced in RA patients (all P < 0.001). Moreover, ZFAS1 expression was negatively associated with CRP in RA patients (P = 0.002). In summary, ANRIL, lnc-DC, MALAT1 , and ZFAS1 genes SNPs were not associated with RA susceptibility, while altered ANRIL, lnc-DC, MALAT1, ZFAS1 levels in RA patients suggested that these lncRNAs might play a role in RA. [ABSTRACT FROM AUTHOR]

Purpose Of the Study: Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility.Study Design: We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA.Results: The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes.Conclusions: The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results. [ABSTRACT FROM AUTHOR]

Objective:This study was performed to systematically summarize the results on the association ofHLA-DQB1polymorphisms with pemphigus vulgaris (PV) and other related factors. Methods:A comprehensive literature search of PubMed, The Cochrane Library, Embase, and Google Scholar database was conducted to identify relevant articles in English, with the last report up to November 1, 2016. Heterogeneity test was performed, and publication bias was evaluated. Stata software 12.0 was used to perform the meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CI) were used to describe the correlation by random-effects model. Results:18 studies were obtained after searching databases: 10 studies were about Caucasian, and 8 articles were about non-Caucasian. Meta-analysis revealed that the allele and phenotype frequencies ofDQB1 05were markedly higher in PV patients than in controls [P < 0.001, OR: 2.640, 95%CI: 1.570–4.441;P = 0.030, OR 3.688, 95%CI: 1.138–11.946]. In addition,DQB1 03was significantly increased at the allele level [P < 0.001, OR: 2.080, 95%CI: 1.507–2.869], andDQB1 02was significantly decreased in PV at the allele and phenotype levels [P = 0.002, OR: 0.450, 95%CI: 0.289–0.702;P = 0.001, OR: 0.293, 95%CI: 0.146–0.587]. When based on each subtype ofHLA-DQB1, DQB1 05:03andDQB1 03:02may play susceptibility roles in PV, andDQB1 03:03, DQB1 05:01andDQB1 06:01are negatively associated with PV. Conclusion:In summary, our study suggests that alleles from the groupsDQB1 05andDQB1 03, concretelyDQB1 05:03andDQB1 03:02, respectively, may be the susceptibility factors for PV at allele and phenotype levels, whereasDQB1 05:01, DQB1 02, DQB1 06:01, andDQB1 03:03are negatively associated with PV. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether X‐ray repair cross‐complementing group 1 (XRCC1) gene polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta‐analysis was conducted to determine the associations between XRCC1 gene polymorphisms and susceptibility to SLE and RA. Methods: A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Results: A total of nine case‐control articles, consisting of five SLE and four RA articles, involving 1138 patients and 1399 healthy controls, were included in the meta‐analysis. This meta‐analysis showed no significant association of the Arg399Gln and Arg194Trp polymorphisms with SLE were found in all models when all study subjects were considered together. Stratification by ethnicity indicated the variant Arg399 (A) allele carriers increased the risk of SLE in Asians (A vs. G: OR = 1.402, 95% CI = 1.139–1.726, P = 0.001) and decreased the risk of SLE in Caucasians (A vs. G: OR = 0.769, 95% CI = 0.630–0.937, P = 0.009; AA vs. AG+GG: OR = 0.727, 95% CI = 0.554–0.953, P = 0.021). However, we failed to reveal any association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk under all analysis models. Similar results were obtained in the subgroup analysis based on ethnicity. Conclusions: The present study suggests that the XRCC1 Arg399Gln polymorphism might be associated with genetic susceptibility to SLE in Asians and Caucasians, and there is no significant association between XRCC1 gene polymorphisms (Arg399Gln, Arg280His and Arg194Trp) and RA risk. [ABSTRACT FROM AUTHOR]

Aim: Studies investigating the association between HLA-DQB1 alleles and rheumatoid arthritis (RA) have reported conflicting results. The purpose of this study was to evaluate whether DQB1 alleles confer susceptibility to RA.Design: A comprehensive literature search up to May 2016 was conducted to identify case-control studies on the association of HLA-DQB1 alleles with RA. Pooled ORs with 95% CIs were used to assess the strength of association.Setting: The literature indicates that HLA-DQB1 is associated with susceptibility to RA.Main Outcome Measures: Frequencies of HLA-DQB1 alleles and phenotype in RA patients and healthy controls.Results: Fifteen studies with 1250 cases and 1621 controls were included in this meta-analysis. DQB1 alleles were associated with RA susceptibility. The frequencies of DQB1*06 were lower in RA (p-value for comparability=0.007, OR 0.726,95% CI 0.576 to 0.916; p=0.004, OR 0.611,95% CI 0.438 to 0.852). The frequencies of DQB1*02 were lower in RA (p=0.044, OR 0.731,95% CI 0.597 to 0.895). A higher frequency of DQB1*04 was observed in RA (p=0.023, OR 1.604,95% CI 1.067 to 2.410).Conclusions: This meta-analysis demonstrates that DQB1*02 and DQB1*06 may be negatively associated with RA. Conversely, DQB1*04 may confer susceptibility to RA. [ABSTRACT FROM AUTHOR]

To explore the association of LEP and leptin receptor ( LEPR) gene single-nucleotide polymorphisms ( SNPs) with susceptibility to systemic lupus erythematosus ( SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction ( iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis ( P = 0.012, P = 0.011, respectively). In LEPR, the GA/ AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE ( P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE ( P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between the single-nucleotide polymorphisms (SNPs) of interleukin 10 alpha receptor ( IL10RA) gene and rheumatoid arthritis (RA) in a Chinese population. We examined 533 RA patients and 958 subjects as a control group. Three IL-10RA SNPs (rs9610, rs2229113 and rs3135932) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The IL-10RA rs9610 A allele was increased in patient group compared with control subjects (OR = 1.232, 95 % CI = 1.052-1.442, p = 0.030). Significant difference in genotype distribution was found in RA patients and controls (χ2 = 15.32, p < 0.001). We also discovered a statistical significance under the dominant model (GG + AG versus AA: OR = 0.676, 95 % CI = 0.546-0.837, p < 0.001). However, no significant difference was discovered in the recessive model (GG versus AG + AA: OR = 1.013, 95 % CI = 0.754-1.361, p = 0.932). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs9610 between anti-CCP positive patients and anti-CCP negative patients (χ2 = 7.209, p = 0.007; χ2 = 9.061, p = 0.011; respectively). We also found a significant difference in genotype frequency at rs9610 in females compared with males (χ2 = 7.658, p = 0.022). Unfortunately, we failed to find any significant results between two IL-10RA SNPs (rs2229113 and rs3135932) and RA susceptibility. The findings suggest that IL-10RA rs9610 polymorphism might contribute to RA susceptibility. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to analyze the association of two single nucleotide polymorphisms (SNPs) in Peli-1 gene with systemic lupus erythematosus (SLE) in a Chinese population. Methods: We conducted a case–control study and a total of 738 SLE patients and 827 healthy controls were finally recruited. Peli-1 rs329498 and rs10496105 polymorphisms were specified from genomic DNA using TaqMan genotyping assay on Fluidigm 192.24 system. Results: Allele contrast showed the minor allele C was associated with decreased risk for SLE when compared with the A allele (OR = 0.851, 95% CI = 0.737–0.983,p= 0.028). Significant difference was observed in genotype distribution of rs329498 polymorphism between lupus nephritis (LN) patients and non-LN patients (χ2= 8.18,p= 0.017). Furthermore, we also found a decreased frequency of the minor allele C in LN patients (29.2%) than in non-LN patients (37.7%) (χ2= 8.67,p= 0.003). Moreover, a significant difference was also detected under a dominant model with regard to the distribution of genotype frequencies between LN patients and non-LN patients (CC + AC vs. AA: OR = 0.632, 95% CI = 0.451–0.884,p= 0.007). Clinical features analysis showed a significant difference in the distribution of genotypic frequencies between patients with malar rash and patients without this feature (χ2= 6.63,p= 0.036). Unfortunately, we failed to find any significant results between Peli-1 gene rs10496105 and SLE susceptibility. Conclusions: Our observations suggested that Peli-1 gene polymorphism rs329498 might contribute to SLE susceptibility in Chinese Han Population. Likewise, the rs329498 SNP was also associated with the clinical features LN and malar rash in SLE patients. [ABSTRACT FROM PUBLISHER]

Objective: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute. Methods: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR = 0.813, 95%CI = 0.694–0.953,p = 0.010) in overall populations. Conclusions: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions. [ABSTRACT FROM PUBLISHER]

In our previous study, we found that glucocorticoid receptor (GR) gene genetic polymorphisms may play a major role in the efficacy of glucocorticoids (GCs) in Chinese systemic lupus erythematosus (SLE) patients. The aim of this study is to explore the association of GR gene genetic polymorphisms and improvement of health-related quality of life (HRQOL) in Chinese SLE patients treated with GCs. A total of 195 Chinese SLE patients were treated with GCs for 12 weeks. The HRQOL of patients was measured with the Medical Outcomes Study Short Form-36 (SF-36) at baseline and 12 weeks. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. One hundred eighty-four patients (94.36 %) completed the 12-week follow-up. Twenty-three single-nucleotide polymorphisms of GR gene were genotyped. There was a significant association between rs10482672 polymorphism and improvement in physical function ( P = 0.043), general health ( P = 0.024), and social function ( P = 0.013). The rs12656106 polymorphism was associated with improvement in the total score of SF-36 ( P = 0.014), physical function ( P = 0.013), general health ( P = 0.010), vitality ( P = 0.015), social function ( P = 0.004), physical component summary ( P = 0.016), and mental component summary ( P = 0.014). The rs4912905 polymorphism was associated with improvement in bodily pain ( P = 0.040) and general health ( P = 0.038). The rs4912911 polymorphism was associated with improvement in general health ( P = 0.026) and vitality ( P = 0.027). The rs4986593 polymorphism was associated with improvement in bodily pain ( P = 0.034). The rs7719514 polymorphism was associated with improvement in vitality ( P = 0.002) and mental component summary ( P = 0.041). We also found a significant association between rs9324924 polymorphism and improvement in physical function ( P = 0.040), bodily pain ( P = 0.007), and general health ( P = 0.019). These results indicate that there may be an association of GR gene rs10482672, rs12656106, rs4912905, rs4912911, rs4986593, rs7719514, and rs9324924 polymorphisms with improvement of HRQOL in Chinese SLE patients treated with GCs. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the associations of lymphotoxin alpha ( LTA) 252 A>G polymorphism (rs909253) with systemic lupus erythematosus ( SLE) and rheumatoid arthritis ( RA) risk. Method Data were collected from the following electronic databases, including EMBASE, PubMed and China National Knowledge Infrastructure ( CNKI). A total of 19 studies (13 studies involving 1346 SLE patients and 1951 controls, six studies involving 1079 RA patients and 1057 controls) were included. Results This meta-analysis showed no evidence of significant association of the A allele with SLE susceptibility (odds ratio [ OR] 1.26; 95% confidence interval [ CI] 0.98-1.62, P = 0.073), but it showed a weaker association under an additive model ( OR 1.63, 95% CI 1.01-2.65, P = 0.047). Stratification by ethnicity indicated that the variant A allele carriers increased the risk of SLE in Asians ( OR 1.91, 95% CI 1.44-2.53, P < 0.001). However, we failed to reveal any association between LTA gene 252 A>G polymorphism and RA risk under all models (for A vs. G: OR 1.02, 95% CI 0.79-1.33, P = 0.853; for AA + AG vs. GG: OR 0.86, 95% CI 0.52-1.41, P = 0.542; for AA vs. AG + GG: OR 1.19, 95% CI 0.80-1.78, P = 0.394, for AA vs. GG: OR 1.03, 95% CI 0.58-1.84, P = 0.919). Similar results were obtained in the subgroup analysis based on ethnicity. Conclusion The present study suggests that LTA 252 A>G polymorphism is associated with SLE susceptibility in Asians, and there is no significant association between LTA 252 A>G polymorphism and RA. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with susceptibility to inflammatory bowel disease (IBD). Methods: Relevant studies were searched using PubMed and Embase up to February 2014. A meta-analysis was conducted on the association between rs2043211 polymorphism and IBD using: (1) allele contrast, (2) the dominant model, (3) the recessive model, and (4) homozygote contrast. The pooled estimated of risk was obtained by random-effects model or fixed-effects model. Publication bias was assessed by Egger's test. Results: Eight relevant articles with a total of 10 534 IBD patients [6785 Crohn's disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis (IC)] and 6755 healthy controls were included in the meta-analysis, which consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant association between rs2043211 polymorphism and IBD, CD, and IC in overall population. However, stratified meta-analysis by ethnicity showed significant association between rs2043211 polymorphism and CD in the European population under the dominant model [odds ratio (OR) = 1.210, 95% confidence interval (CI) = 1.013-1.445, p = 0.036] and homozygote contrast (OR = 1.212, 95% CI = 1.005-1.461, p = 0.044). Conclusions: Our meta-analysis results indicated significant association between rs2043211 polymorphism and the susceptibility to CD under the dominant model and homozygote contrast in the European population. [ABSTRACT FROM AUTHOR]

Objectives: Previous published data indicated that interleukin-21 (IL-21) gene polymorphisms were shown to associate with multiple autoimmune diseases (ADs), but the results remain inconclusive. The aim of this study was to perform a meta-analysis to assess the overall association between IL-21 gene polymorphisms (rs907715, rs2221903) and multiple ADs. Methods: All eligible case-control studies were searched in the PubMed and Embase database. A meta-analysis was conducted on the association between the IL-21 gene variants and ADs using: (1) allelic contrast, (2) homozygote contrast, (3) the recessive model, and (4) the dominant model. Results: A total of 12 relevant studies including 10 535 cases and 19 356 controls were enrolled in this meta-analysis. A significant association between IL-21 rs907715 gene polymorphism and AD was found under the allelic (OR: 1.102, 95% CI: 1.057-1.149, p = 0.000), homozygous (OR: 1.220, 95% CI: 1.089-1.368, p = 0.001), dominant (OR: 1.160, 95% CI: 1.027-1.309, p = 0.017), and recessive genetic model (OR: 1.119, 95% CI: 1.055-1.187, p = 0.000) among Caucasian populations. However, there was no significant association between IL-21 rs2221903 polymorphism and AD in different genetic models. Conclusions: Data from the present study suggest that the IL-21 rs907715 polymorphism might be associated with multiple ADs susceptibility in Caucasians. Especially, the allele G of intronic rs907715 in IL-21 confers increased risk of ADs. [ABSTRACT FROM AUTHOR]

Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057–1.429, and P=0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598–0.850, and P<0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137–1.830, and P=0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians. [ABSTRACT FROM AUTHOR]

The results of studies on association between FCGR2A- R/H131 polymorphism and susceptibility to systemic lupus erythematosus (SLE) in the Asian population are controversial. To derive a more precise estimation on the genetic risk of FCGR2A- R/H131 variant for SLE in Asians, a meta-analysis was performed for genotypes R/R + R/H (dominant effect), R/R (recessive effect), and R allele in fixed/random effects models. Twenty studies involving 4,832 SLE patients and 6,190 controls were included. The meta-analysis showed that FCGR2A- R/H131 variant was associated with development of SLE in overall Asians both at allele or genotype level (R vs H, OR 1.201, 95 % CI 1.098-1.315; RR + RH vs HH, OR 1.369, 95 % CI 1.115-1.682; RR vs RH + HH, OR 1.305, 95 % CI 1.029-1.654). After stratification by ethnic, a significant association of R allele with susceptibility to SLE was observed in the Chinese population (R vs H, OR 1.104, 95 % CI 1.030-1.183). Evidence from subgroup analyses in non-Chinese populations (all Asians excluding Chinese population) also showed a significant association (R vs H, OR 1.354, 95 % CI 1.207-1.519; RR + RH vs HH, OR 1.705, 95 % CI 1.234-2.355). In addition, FCGR2A-R131 allele was associated with a 1.186-fold (95 % CI 1.043-1.349) greater risk for the occurrence of nephritis in the Asians population with SLE. After stratification by ethnic, this significant association was only consistently identified in non-Chinese populations (R vs H, OR 1.220, 95 % CI 1.002-1.486). In summary, FCGR2A- R/H131 polymorphism is associated with SLE and lupus nephritis in Asians. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the cytotoxic T lymphocyte-associated antigen 4 ( CTLA-4) CT60 polymorphism (rs3087243) confers susceptibility to autoimmune thyroid disease (AITDs). Methods: A meta-analysis was performed using: (1) allelic contrast, (2) recessive model and (3) dominant model. Electronic search of PubMed, Medline and Chinese National Knowledge Infrastructure (CNKI) was conducted to select studies. Results: Finally, a total of 20 separate studies were available for the current meta-analysis: Graves' disease (GD): 18 studies including 1 Iranian, 6 Caucasian and 11 Asian populations; Hashimoto's thyroiditis (HT): seven studies including one Iranian, three Caucasian and three Asian populations. A significant association was found between the CTLA-4 CT60 polymorphism (rs3087243) and GD, with regard to comparisons between allele and genotype frequencies (all p < 0.001). After stratification by ethnicity, significant relationships were consistently identified both in Caucasian and Asian populations. Furthermore, the association between this allelic variant and HT risk was also found in overall and Asian populations (OR: 1.26, 95% CI: 1.10-1.44; OR: 1.45, 95% CI: 1.19-1.76, respectively). Conclusion: Taken together, our study suggested that the CT60 polymorphism (rs3087243) in CTLA-4 gene might confer susceptibility to the AITDs (GD/HT). [ABSTRACT FROM AUTHOR]

Objective. Vitamin D receptor (VDR) gene polymorphisms may be associated with the risk of OA, however, evidence for this is controversial. This meta-analysis aims to confirm whether VDR gene polymorphisms are associated with OA.Methods. Meta-analyses on the association between OA and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allele and homozygote contrast and contrasts in the recessive and dominant models. Stratification analyses by different demographic regions (Europe vs Asian) were also performed and pooled odds ratios (ORs) were obtained using the random effects model if the results were heterogeneous.Results. A total of 13 relevant studies involving OA patients (n = 2104) and controls (n = 2939) were included in the analysis. There were significant associations between VDR ApaI polymorphisms and OA in the Asian population (A vs a: OR = 1.16, 95% CI 1.02, 1.32, P = 0.025; AA vs Aa/aa: OR = 1.36, 95% CI 1.04, 1.77, P = 0.025; AA vs aa: OR = 1.35, 95% CI 1.00, 1.80, P = 0.047), but not in the whole population. There was also a statistically significant association between FokI polymorphism and OA (FF vs Ff/ff: OR = 0.65, 95% CI 0.44, 0.95, P = 0.024); however, this result was derived from only two studies. No significant associations were found between VDR TaqI and BsmI polymorphisms and OA.Conclusion. There are modest but statistically significant associations between VDR ApaI polymorphisms and the susceptibility of OA in the Asian population. [ABSTRACT FROM PUBLISHER]

Systemic lupus erythematosus (SLE) is complex autoimmune disease which involves various facets of the immune system. Signaling transducers and activators of transcription 1 (STAT1) belongs to the family of STAT transcription factors that mediate various biological responses. Recently, studies in both experimental animal models of lupus and patients with SLE have revealed expression and activation of STAT1 is closely associated with the pathogenesis of SLE. Moreover, increased production of interferons (IFNs) and aberrant activation of IFNs signaling, which is mechanistically linked to increased level of STAT1, are crucial for the development of SLE. Therefore, we will focus on the association of STAT1 and SLE based on recent understandings to render more information about the mechanisms of STAT1 might perform in. Hopefully, the information obtained will lead to a better understanding of the development and pathogenesis of systemic autoimmune diseases, as well as its clinical implications and therapeutic potential. [ABSTRACT FROM AUTHOR]

Aims To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. Methods The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms ( SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form ( CTQ- SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression. Results A functional polymorphism at 3′ UTR of the corticotropin-releasing hormone receptor 1 ( CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission. Conclusions Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor 1 (HIF-1) introduced the immune imbalance between Th17 and Treg cells, which may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of the present study was to determine whether the HIF1A gene influences the susceptibility to SLE. A study on this relationship has not been conducted to date. A total of 3,793 subjects (1,497 SLE patients and 2,296 controls) were included in this study. The genotyping of five single-nucleotide polymorphisms (SNPs) (rs11549465, rs12434438, rs1957757, rs1951795, rs7143164) was determined by Sequenom MassARRAY technology. The statistical analysis was conducted using chi-square test. Odds ratio (OR) with 95 % confidence interval (CI) was calculated using unconditional logistic regression with adjustment of age and sex. The allele frequencies were not associated with the disease. No significant differences in genotype frequencies existed between the patients with SLE and the controls in all five SNPs. It is worth mentioning that the allele T at rs11549465, located at the exon sequence, revealed a trend but no significant difference towards the more frequent allele T in SLE than in controls (C versus T: OR = 1.206, 95 % CI = 0.972-1.495, p = 0.088). The genotype effects of recessive, dominant, and codominant models were observed; however, no significant evidence for association was detected. Our findings suggest that the gene polymorphisms of HIF1A might not contribute to SLE susceptibility in the Chinese population. However, further studies are needed on an independent cohort from different genetic backgrounds to confirm HIF1A as an SLE genetic factor. [ABSTRACT FROM AUTHOR]

The response to glucocorticoids (GCs) for patients with systemic lupus erythematosus (SLE) is characterized by wide interindividual variability, with a significant number of patients who have no response. We analyzed whether genetic polymorphisms within glucocorticoid receptor (GR) gene are related to variability in the efficacy of GCs in Chinese population with SLE. A cohort of 220 patients with SLE was studied. These patients were treated with GCs (prednisone) for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index (SLEDAI). Patients were classified into two groups (sensitive and insensitive) according to their response to GCs. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. A total of 212 patients (96.4%) were included in the final data analyses. Of these patients, 110 patients were considered sensitive to GCs, and 102 patients were considered insensitive to GCs. Eighteen tag single nucleotide polymorphisms (SNPs) of GR gene were selected. Significant associations were seen for rs4912905 (dominant model: crude OR = 0.410, 95%CI = 0.233-0.722, p = 0.002; adjusted OR = 0.419, 95%CI = 0.233-0.754, p = 0.004), rs17100234 (dominant model: crude OR = 0.521, 95%CI = 0.282-0.963, p = 0.038; adjusted OR = 0.520, 95%CI = 0.279-0.970, p = 0.040) and rs7701443 (recessive model: crude OR = 2.736, 95%CI = 1.183-6.331, p = 0.019; adjusted OR = 2.639, 95%CI = 1.116-6.239, p = 0.027) in GR gene, but not for other polymorphisms ( p > 0.05). The results of the present study suggest that GR genetic polymorphisms may play a major role in the efficacy of GCs in Chinese population with SLE. [ABSTRACT FROM AUTHOR]

Interleukin-10 (IL-10) is a pleiotropic cytokine and plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Unlike IL-10 protein, few studies have focused on the potential association between IL-10 receptor (IL-10R) and SLE. The purpose of this study was to examine the association of a single nucleotide polymorphism, rs2834167 (A/G), in IL-10R2 gene (IL-10RB) with SLE in a Chinese Han population. A total of 667 patients with SLE and 676 healthy controls were enrolled in the present study. IL-10RB rs2834167 (A/G) polymorphism was specified from genomic DNA using TaqMan genotyping assay on a 7300 real-time reverse transcription polymerase chain reaction system. We found that the frequency of A allele for rs2834167 in patients (44.53 %) was significantly higher than in controls (40.16 %) ( χ = 5.24, P = 0.022). Allele A was associated with a 1.196-fold (95 % confidence interval (CI), 1.026-1.394) greater risk for the occurrence of SLE compared with the G allele. And both genotypes AG and AA were associated with the susceptibility to SLE as compared with the GG genotype (AG versus GG, odds ratio (OR) = 1.332; 95 %CI, 1.047-1.696; AA versus GG, OR = 1.373; 95 %CI, 1.004-1.878). We also found a statistical significance in the dominant model (AA + AG versus GG, OR = 1.343; 95 %CI, 1.070-1.687). However, no significant evidence for the association of IL-10RB rs2834167 (A/G) polymorphism with any clinical manifestations was detected. Our observations indicate that IL-10RB rs2834167 (A/G) polymorphism may be a potential biomarker for susceptibility to SLE. [ABSTRACT FROM AUTHOR]

The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the association of interleukin-1 (IL-1), IL-10 and tumor necrosis factor (TNF)-α polymorphisms with Behcet's disease (BD). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 4003 cases and 4748 controls in 19 eligible studies were included in the meta-analysis. We examined the relationship between seven single nucleotide polymorphisms (SNPs) in the above-mentioned three cytokine genes and susceptibility to BD. Meta-analysis indicated the association between the cytokine gene polymorphisms in all study subjects in the allelic model (TNF-α -308A/G: OR = 0.73, 95% CI: 0.61-0.88, P = 0.001; IL-10 -819C/T: OR = 0.72, 95% CI: 0.66-0.78, P < 0.001; IL-10 -592C/A: OR = 0.74, 95% CI: 0.64-0.86, P < 0.001); the dominant model (TNF-α -308A/G: OR = 0.77, 95% CI: 0.64-0.92, P = 0.004; IL-10 -1082G/A: OR = 1.64, 95% CI: 1.10-2.44, P = 0.014); the recessive model (TNF-α -308A/G: OR = 0.27, 95% CI: 0.12-0.65, P = 0.003; IL-10 -819C/T: OR = 0.71, 95% CI: 0.57-0.90, P = 0.004). However, no significant evidence for the associations of IL-1a -889C/T, IL-1b -551C/T, IL-1b -3962C/T polymorphisms with BD susceptibility was detected. The present study might suggest that TNF-α -308A/G, IL-10 -1082G/A, -819C/T, -592C/A polymorphisms are associated with BD susceptibility. [ABSTRACT FROM AUTHOR]

Objective: The aim to this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of interleukin ( IL)- 23 receptor gene and systemic lupus erythematosus (SLE) in a Chinese population. Methods: A case-control study was performed to investigate the associations of SNPs in IL- 23R gene (rs10889677 and rs1884444) with susceptibility to SLE in 521 Chinese SLE patients and 527 normal controls. The chi-square test and unconditional Logistic regression were used to analysis by SPSS 10.1 software. Results: No significant differences were detected for the distribution of allele and genotype frequencies of these two SNPs between patients and controls as well as SLE patients with nephritis (LN) and those without nephritis. Conclusion: The findings suggest that the polymorphisms of IL- 23R gene might not contribute to the susceptibility of SLE in the Chinese population. [ABSTRACT FROM AUTHOR]

The P2X7 receptor is a ligand-gated cationic channel receptor that is actived by ATP and normally expressed by a variety of immune system cells, including macrophages and lymphocytes. Because it leads to release of IL-1β and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of autoimmune inflammatory diseases, such as systemic lupus erythematosus (SLE). The P2X7R gene is highly polymorphic, and many single-nucleotide polymorphisms (SNPs) have been detected. A case–control study was performed to investigate the associations of SNPs in the P2X7R gene (rs1718119, rs2230911 and rs3751143) with susceptibility to SLE in 535 Chinese SLE patients and 532 controls. Results showed that rs1718119 was associated with SLE; in particular carriers of the A allele and AA/AG/(AG+AA) genotypes were at lower risk of the disease [A versus G, P < 0.001, odds ratio (OR) = 0.543, 95% CI: 0.424–0.697; AG versus GG, P = 0.018, OR = 0.659, 95% CI: 0.466–0.931; AA versus GG, P = 0.011, OR = 0.176, 95% CI: 0.046–0.668; AG+AA versus GG, P = 0.004, OR = 0.607, 95% CI: 0.433–0.850], but no significant differences in rs2230911 and rs3751143 were observed between SLE patients and controls. Stratification of cases for the presence of nephritis showed that rs2230911 G allele and CG/(CG+GG) genotypes were at a lower risk of SLE with nephritis (LN) (G versus C, P = 0.011, OR = 0.640, 95% CI: 0.454–0.903; CG versus CC, P = 0.035, OR = 0.645, 95% CI: 0.429–0.970; GG versus CC, P = 0.101, OR = 0.349, 95% CI: 0.099–1.228; CG+GG versus CC, P = 0.015 OR = 0.612, 95% CI: 0.411–0.910), but rs1718119 and rs3751143 were not associated with LN. Analysis of the haplotypes revealed one haplotype (ACA) that appeared to be a significantly ‘protective’ haplotype (P = 0.009, OR = 0.708, 95% CI: 0.546–0.918) with SLE. The findings suggest that the P2X7R gene might contribute to SLE susceptibility in the Chinese population. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex autoimmune disease arising from the action of multiple genetic and environmental risk factors. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs1990760, of the interferon induced with helicase C domain 1 ( IFIH1) gene with SLE in a Chinese population. A total of 877 SLE patients and 978 healthy control subjects were enrolled in the present study. The genotype of the IFIH1 rs1990760 polymorphism was determined by Sequenom MassARRAY technology. The IFIH1 rs1990760 T allele was significantly increased in patient group compared with control subjects (T versus C, Odds ratio = 1.20, 95 % confidence interval = 1.02-1.40). However, no significant difference in genotype distribution was found between cases and controls ( P = 0.07). No significant evidence was detected for the association of the IFIH1 rs1990760 polymorphism with SLE under neither dominant nor recessive model (TT + TC versus CC, P = 0.06; TT versus TC + CC, P = 0.08). We also analyzed the association of the IFIH1 rs1990760 T allele with clinical features, whereas no significant signal was found. In conclusion, our study represents the first report demonstrating an association of the IFIH1 rs1990760 polymorphism with SLE susceptibility in a Chinese population. [ABSTRACT FROM AUTHOR]

Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) -1722T/C polymorphism has been identified as a susceptibile gene for systemic lupus erythematosus (SLE), but studies are inconsistent. To better assess the association between CTLA-4 -1722T/C polymorphism and SLE, a meta-analysis was performed, including 10 studies, total of 1 387 patients and 1 617 controls. Overall, the CTLA-4 -1722T/C polymorphism was significantly associated with SLE susceptibility (T VS C: OR = 1.17, 95% CI = 0.86-1.60, P = 0.304; T/T VS C/C: OR = 1.92, 95% CI = 1.09-3.39, P = 0.024; T/C VS C/C: OR = 1.50, 95% CI = 0.91-2.49, P = 0.114; T/T VS T/C: OR = 1.29, 95% CI = 0.95-1.75, P = 0.107). When stratified by ethnicity, the CTLA-4 -1722T/C polymorphism was associated with SLE only in Asians (T VS C: OR = 1.47, 95% CI = 1.10-1.96, P = 0.010; T/T VS C/C: OR = 2.09, 95% CI = 1.13-3.85, P = 0.018; T/C VS C/C: OR = 1.53, 95% CI = 0.87-2.69, P = 0.141; T/T VS T/C: OR = 1.42, 95% CI = 0.97-2.09, P = 0.070). In summary, the CTLA-4 -1722T/C polymorphism confers to SLE risk, especially in Asians. [ABSTRACT FROM AUTHOR]

C-Jun has been proved as playing an important role in the pathogenesis of tumors, as a main component of Activator protein 1 and c-Jun gene polymorphisms are associated with colorectal cancer. However, the relationship between the c-Jun gene polymorphism and the susceptibility to systemic lupus erythematosus (SLE) has not been known. Our purpose is to evaluate whether the c-Jun gene polymorphism (SNP rs3748814) is associated with susceptibility to SLE in a Chinese population. In this study, we enrolled 502 SLE patients and 652 healthy controls. The c-Jun polymorphism (rs3748814) was specified from genomic DNA using the TaqMan genotyping assay on a 7300 real-time reverse transcription polymerase chain reaction system. We found that the frequency of the A/G genotype in SLE patients was lower than in healthy controls, whereas the frequency of the G/G genotype was significantly higher in SLE patients than in healthy controls (A/G vs. G/G p=8.670e-08, odds ratio [OR]=0.290, 95% confidence interval [CI]=0.184-0.456). In addition, the frequency of allele A in the patients group was significantly lower than in the control group (A vs. G p=5.221e-09, OR=0.308, 95% CI=0.212-0.466). The distribution of genotype and allele frequency in SLE patients with lupus nephritis (LN) compared with SLE patients without LN was not statistically significant (A/G vs. G/G p=0.744, OR=1.157, 95% CI=0.481-2.785; A vs. G p=0.748, OR=1.152, 95% CI=0.486-2.734; A/A+A/G vs. G/G p=0.744, OR=1.157, 95% CI=0.481-2.785). Furthermore, we did not find any significant association between other clinical features and genotypes. Our findings suggest that the c-Jun polymorphism (rs3748814) may be significantly associated with the susceptibility to SLE in a Chinese population. [ABSTRACT FROM AUTHOR]

Recently, protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism has been identified as a susceptibile gene for type 1 diabetes (T1D), but studies are inconsistence, In order to assess the association between PTPN22C1858T polymorphism and T1D based on different ethnicities, a meta-analysis was performed, including 26 studies, total of 16,240 patients and 17,997 controls. Meta-analysis was performed on T versus C, T/T+T/C versus C/C (dominant model) and T/T versus T/C+C/C (recessive model) in a fixed/random effects model. The results indicated an association between the PTPN22 C1858T polymorphism and T1D in all subjects. The overall odds ratio ( OR) of T versus C using the fixed effects model was 1.948 (95% CI = 1.859∼2.041, P < 0.001). After stratification by ethnicity, analysis revealed that the PTPN22 C1858T polymorphism T allele was significantly associated with T1D in Europeans, Americans ( OR = 1.946, 95% CI = 1.852∼2.045, P < 0.001; OR = 1.946, 95% CI = 1.690∼2.242, P < 0.001, respectively). Meta-analysis of the T/T+T/C genotype and the T/T genotypes showed the same results as that shown by the PTPN22 C1858T polymorphism T allele. This meta-analysis suggests a possible association between the PTPN22 C1858T polymorphism and T1D, especially in European and American populations. [ABSTRACT FROM AUTHOR]

Published data on the association between tumor necrosis factor-alpha (TNF-α) promoter-308 A/G polymorphism and systemic lupus erythematosus (SLE) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 28 studies including 2,992 cases and 4,326 controls (5,924 cases and 8,484 controls in A versus G comparison) were involved in this meta-analysis. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. In addition, we also performed a 'model-free' analysis by considering the G/G genotype as the reference and estimated the OR for the A/A versus G/G and A/G versus G/G genotype. Overall, an association of TNF-α promoter-308 A/G polymorphism with SLE was found (A versus G: OR = 1.686, 95% CI = 1.400-2.032, P < 0.001; A/A versus A/G+G/G: OR = 3.043, 95% CI = 2.185-4.238, P < 0.001; A/A+A/G versus G/G: OR = 1.822, 95% CI = 1.379-2.407, P < 0.001; A/A versus G/G: OR = 3.686, 95% CI = 2.628-5.172, P < 0.001; A/G versus G/G: OR = 1.691, 95% CI = 1.291-2.215, P < 0.001). However, stratification by ethnicity indicated that the risk A allele was not associated with SLE in Asian (A versus G: OR = 1.207, 95% CI = 0.856-1.702, P = 0.283) and African population (A versus G: OR = 1.225, 95% CI = 0.597-2.516, P = 0.580). In summary, this meta-analysis indicated that TNF-α promoter-308-A/G polymorphism is associated with susceptibility to SLE. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of receptor interacting protein 2 (RIP2) single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A case–control study was performed on the SNPs rs16900617 and rs16900627 in 590 Chinese SLE patients and 660 healthy controls. These SNPs were typed by TaqMan allele discrimination assays. We found a significant association of rs16900617 G allele [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.41–0.72] and rs16900627 G allele (OR = 1.28, 95% CI 1.04–1.58) with SLE. Significant differences in genotype frequency distribution were also found in SLE and control individuals (rs16900617: AG versus AA, OR = 0.59, 95% CI 0.44–0.81; GG versus AA, OR = 0.08, 95% CI 0.01–0.65; AG + GG versus AA, OR = 0.55, 95% CI 0.41–0.75; rs16900627: AG versus AA, OR = 1.51, 95% CI 1.17–1.93; AG + GG versus AA, OR = 1.43, 95% CI 1.13–1.82). Analysis of the haplotypes revealed that two haplotypes of AG and GA were also significantly associated with SLE (OR = 1.37, 95% CI 1.11–1.70; OR = 0.60, 95% CI 0.45–0.79). Our findings suggest that the RIP2 gene polymorphisms may be associated with susceptibility to SLE in the Chinese population. [ABSTRACT FROM PUBLISHER]

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune diseases, which affects multiple organ systems such as kidney. The imbalance of T-helper 1 (Th1)/Th2 cells is critical in the pathogenesis of SLE. The T-cell immunoglobulin mucin (TIM) proteins comprise a family of cell surface molecules expressed on T cells that regulate Th1- and Th2-cell-mediated immunity. Recent work has found increased expression of TIM-1 and TIM-3 ligand (galactin-9) mRNA in SLE patients and implied that TIM proteins might be involved in the pathogenesis of SLE. In this study, genotyping of single-nucleotide polymorphisms (SNPs) was performed for TIM-1 (rs1501909 and rs12522248) and TIM-3 (rs9313439 and rs10515746) in 202 SLE patients and 217 healthy individuals in a Chinese population. Results showed no significant differences existed between the patients with SLE and the controls as well as SLE patients with nephritis and those without nephritis, in all four SNPs. The findings suggest that the polymorphisms of TIM gene family might not contribute to SLE susceptibility in the Chinese population. However, it should be noted that the statistical power of our study is relatively low, which likely did not have adequate power to detect the actual correlation between the selected SNPs and SLE susceptibility; moreover, we cannot discard a possible association of other variants within the region covering TIM with SLE as a genetic risk factor, with larger samples in different populations. [ABSTRACT FROM AUTHOR]

Abstract: The aim of our meta-analysis was to assess the association between BDNF Val66Met polymorphism and treatment response in patients with MDD. 8 studies that included data from 1115 subjects were identified. We tested two phenotypes: response rate and remission rate. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for genotypes Met/Met versus Val/Val, Val/Met versus Val/Val, Met/Met versus Val/Met, Val/Met+Met/Met versus Val/Val, Met/Met versus Val/Val+Val/Met, and Met allele versus Val allele. When all groups were pooled, a significant association of Val/Met genotype and increased response rate was found in comparison to Val/Val in overall population (OR=1.66, 95%CI=1.07–2.57, P =0.02). In the subgroup analysis, similar result was shown in Asian population (OR=1.83, 95%CI=1.03–3.26, P =0.04), but not in Caucasian population. We didn''t observe a significant association of BDNF Val66Met polymorphism with remission rate. This meta-analysis demonstrates the association between BDNF Val66Met polymorphism and treatment response in patients with MDD, and Val66Met heterozygous patients have a better response rate in comparison to Val/Val homozygote patients, especially in Asian population. [Copyright &y& Elsevier]

The tumor necrosis factor-α (TNF-α) promoter − 238A/G polymorphism has been repeatedly associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. Our aim was to do a meta-analysis to assess the association between TNF-α promoter − 238A/G polymorphism and SLE. Eleven published studies of this polymorphism with SLE in different ethnic groups were identified using a Medline search. Meta-analysis was performed for genotypes AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele in a fixed/random effect model. The overall odds ratio (OR) of the AA versus GG+GA genotypes was 3.46 (95% CI = 1.35–8.83, P = 0.01), and a similar result was found in Caucasian population (OR = 4.62, 95% CI = 1.20–17.80, P = 0.03); the overall OR of the AA versus GG genotypes was 3.36 (95% CI = 1.32–8.55, P = 0.01), and a similar result was found in Caucasian population (OR = 4.29, 95% CI = 1.11–16.53, P = 0.03); the OR of the GA versus GG genotypes was 0.48 (95% CI = 0.30–0.75, P = 0.001) in Caucasian population. In conclusion, this meta-analysis demonstrates the association between TNF-α promoter − 238A/G polymorphism and SLE, especially in Caucasian population. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dispensability of APRIL to development of systemic lupus erythematosus in NZM 2328 mice," by CO Jacob and colleagues in the May 2012 issue.

Objective Both Crohn’s disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk. Methods The PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results A total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR = 0.88, 95% CI = 0.82 ∼ 0.95, P = 0.001; OR = 0.82, 95% CI = 0.76 ∼ 0.89, P < 0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR = 0.85, 95% CI = 0.79 ∼ 0.91, P < 0.001; OR = 0.88, 95% CI = 0.83 ∼ 0.93, P < 0.001), but not with CD susceptibility in Caucasians. Conclusions This meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion. [ABSTRACT FROM AUTHOR]

Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in a Chinese Han population. Four UBASH3A polymorphisms (rs11203203, rs3788013, rs2277798, and rs1893592) were genotyped using the Fluidigm 192.24 Dynamic Array™ Integrated Fluidic Circuit (IFC). Data were analyzed by SPSS 11.5 software. A total of 792 SLE patients and 777 healthy controls were included in this study. The CC genotype and C allele of rs3788013 polymorphism were more frequent in the patient group than in controls (OR = 1.583, 95% CI = 1.095–2.287; OR = 1.258, 95% CI = 1.083–1.461, respectively). We also found a statistical significance under the recessive model (OR = 1.298, 95% CI = 1.049–1.607, p = 0.017). The frequency of variant genotype AC of rs3788013 was associated with the phenotype of vasculitis ( p = 0.012). A statistically significant association was observed between UBASH3A rs1893592 C allele and skin rash, oral ulcer and arthritis ( p < 0.05). Moreover, we found that the genotype distribution of rs2277798 was significantly associated with hematuria in the SLE patients ( p = 0.003). However, UBASH3A rs11203203, rs2277798, and rs1893592 polymorphisms were not associated with the risk of SLE ( p > 0.05). The findings suggest that UBASH3A gene might contribute to SLE susceptibility and influence the clinical phenotype of the disease. Further studies are necessary to elucidate the exact role of UBASH3A gene in the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Background and Aims Studies investigating the association between the peptidylarginine deiminase 4 (PADI4) gene polymorphisms and rheumatoid arthritis (RA) reported conflicting results. The aim of this meta-analysis was to assess the association between PADI4 gene polymorphisms and RA. Methods A systematic literature search was conducted to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Results A total of 34 studies from 28 articles involving 19859 patients with RA and 25771 healthy controls were included. Significant association of PADI4–94G/A polymorphism and RA was observed (OR = 0.891, 95% CI = 0.833–0.954, p = 0.001) in the overall study population and in the Asian populations (OR = 0.824, 95% CI = 0.759–0.894, p = 0.000) respectively. For the –92C/G polymorphism, a significant association was observed (OR = 1.481, 95% CI = 1.166–1.882, p = 0.001) in Africans. For the –90C/T polymorphism, a significant association was observed (OR = 0.576, 95% CI = 0.381–0.872, p = 0.009) in the Latin American population. The pooled estimates for the other polymorphisms were not statistically significantly associated with RA (PADI4–104C/T, –89A/G, –96T/C). Conclusions This meta-analysis demonstrates that PADI4–94G/A polymorphism is associated with susceptibility to RA in the overall population and in the Asian population. The PADI4 –92C/G polymorphism confers susceptibility to RA in Africans and the PADI4–90C/T polymorphism was associated with RA in the Latin American population. [ABSTRACT FROM AUTHOR]