Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations

The association of Fcgamma receptor (FcgammaR) polymorphisms with systemic lupus erythematosus (SLE) has been demonstrated in various populations; however, the results have been inconsistent. We recently identified a single-nucleotide polymorphism encoding a non-synonymous substitution, Ile232Thr (I232T), of FCGR2B and its association with SLE in Japanese and in Thais. Multiple functional FcgammaR genes with polymorphisms (FCGR2A, FCGR2B, FCGR3A, and FCGR3B) cluster in 1q23, and some of them are in linkage disequilibrium (LD). To differentiate contributions from multiple-linked loci, comparison of different populations may provide useful information. In this study, we analyzed the above four FCGR polymorphisms of the Chinese patients and controls for the association with SLE. FCGR2A-H131R, FCGR2B-I232T, FCGR3A-F176V, and FCGR3B genotypes were determined in 167 Chinese patients with SLE and 129 healthy controls. Association was examined using case-control analysis. Allele frequencies of FCGR2B-232T and FCGR3A-176F were significantly increased in SLE [odds ratio (OR) = 1.67 and OR = 1.41, respectively]. Interestingly, while these alleles had a tendency of positive LD in the controls, FCGR2B-232T was in positive association with FCGR3A-176V in SLE, suggesting that these two alleles were associated with SLE in an independent manner. Comparison between SLE with and without nephritis indicated significant association of FCGR2B-232T with nephritis (OR = 2.65). When the present results were combined with our previous data on the Japanese and the Thais using meta-analytic methods, highly significant and independent association was observed for FCGR2B and FCGR3A genotypes. These results strongly suggested that FCGR2B is a common susceptibility factor to SLE in the Asians.     

Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus in Thais

In this study, we investigated the association of HLA-DRB1 and DQB1 with Thai patients with SLE. A highly significant increase in the frequency of DRB1*1502 and DQB1*0501 was found in SLE patients compared with normal controls. DRB1*1501 and DRB1*1602 were also slightly increased. In contrast, DRB1*1202 and DQB1*0301 were decreased, and DRB1*0406 and DRB1*1401 were not found in the patients' group. The haplotype analysis revealed that DRB1*1502 - DQB1*0501 was most strongly associated with SLE, and also suggested a primary role for DRB1 rather than DQB1. Taken together with the previous report which demonstrated the association of the same haplotype in Taiwan, our present observations strongly suggested that DRB1*1502 - DQB1*0501 is the major HLA haplotype that confers susceptibility to SLE in the South-east Asian populations.     

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.     

Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus

The aim of this study was to evaluate the association between systemic lupus erythematosus (SLE) and polymorphisms in the interleukin-23 receptor (IL23R) gene, which have been previously found to be associated with two autoimmune diseases: inflammatory bowel disease and psoriasis. Our study includes 224 SLE patients and 342 healthy controls. The genotyping of IL23R variants was carried out using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assays. No statistically significant differences were observed between SLE patients and healthy controls with any of the IL23R genetic variants. In addition, we did not find any significant differences when we stratified SLE patients according to their clinical and demographic features. These results suggest that IL23R polymorphisms do not appear to play an important role in the susceptibility or severity of SLE in the Spanish population.     

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.     

Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus

Multiple genetic as well as environmental factors are considered to be involved in the development of systemic lupus erythematosus (SLE). A number of previous studies have suggested a possible role for tumor necrosis factor (TNF) in the pathogenesis of SLE. In addition, one of the candidate loci suggested by the genome-wide linkage analysis corresponds to the chromosomal position encompassing the TNF receptor 2 gene (TNFR2). The purpose of this study was to analyze the polymorphism of TNFR2 and its possible association with the susceptibility to SLE, using the case-control association analysis. Polymorphism screening of the exons containing previously reported nonsynonymous base substitutions was carried out by the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method, using genomic DNA from 81 Japanese patients with SLE and 207 healthy individuals. Two alleles were present in exon 6, coding for methionine (196M) and arginine (196R) at position 196. 30 of 81 patients (37.0%) with SLE were positive for the 196R allele, which was significantly more frequent compared with 39 of 207 healthy individuals (18.8%) (chi2=10.6, df=l, P=0.001, odds ratio=2.53, 95% CI: 1.45-4.43). Genotype analysis revealed that the presence of one 196R allele was sufficient for rendering susceptibility. The association of 196R allele with SLE was independent from that of HLA-DRB1*1501. In conclusion, the TNFR2 196R allele was found to be significantly associated with the susceptibility to SLE in the Japanese population. Further population and functional studies will be of particular importance to establish TNFR2 as one of the susceptibility genes to SLE.     

Effects of the programmed cell death 1 (PDCD1) polymorphisms in susceptibility to systemic lupus erythematosus

The failure of immunological tolerance to self‐antigens plays a fundamental role in the pathogenesis of systemic lupus erythematosus (SLE). PD‐1 is an inhibitory receptor for regulating the immune system and preventing development of autoimmune disorders. This study aimed to determine the role of four single‐nucleotide polymorphisms (SNPs) within programmed cell death 1 (PDCD1 or PD‐1) gene and haplotypes defined by these SNPs in susceptibility to SLE in the Iranian population. Blood samples were obtained from 253 SLE and 564 healthy subjects. Red blood cells were lysed and genomic DNAs were extracted using salting‐out method. Genotype determinations of PD1.1, PD1.3, PD1.5 and PD1.9 SNPs were performed by polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP), and 12 haplotypes were constructed by PDCD1 SNPs. Our results showed significant differences in PD1.5 genotype frequencies between patient and control groups (p < .001). The frequencies of PD1.5 C/C, C/T and T/T genotypes versus other genotypes in SLE patients significantly differed from healthy subjects (p < .001, p = .001 and p = .002, respectively). Allelic analysis indicated a significant association between the frequency of PD1.5C allele and development of SLE in our population (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.51–2.42, p < .001). At the haplotype level, GGCC, GACT and GGCT haplotypes were significantly different between SLE and control groups (OR = 2.14, 95% CI = 1.73–2.66, p < .001; OR = 9.76, 95% CI = 4.47–21.3, p < .001; and OR = 0.32, 95% CI = 0.24–0.42, p < .001, respectively). Based on these findings, PD1.5 SNP and some haplotypes of PDCD1 contribute to SLE risk in the Iranian population.     

Association between polymorphisms in the TNF region and systemic lupus erythematosus in the Italian population

The purpose of this work was to test the hypothesis that MHC encoded susceptibility factors for SLE lie in the TNF region. An association study was performed by analyzing 123 northern Italian SLE patients and 199 matched controls for three TNF markers: two polymorphisms in the TNFA promoter and the TNFa microsatellite. Haplotypic combinations of TNF markers were also compared in patients and controls. No significant association was observed considering either the whole SLE panel or SLE clinical and immunological subtypes. Three TNF-238/A homozygous patients were detected, while no homozygote was present in controls. The clinical and immunological phenotype of the three -238/A homozygotes suggests that the -238/AA genotype is a marker of a particular clinical subtype.     

Genetic polymorphisms of CYP2D6 oxidation in patients with systemic lupus erythematosus

Introduction

Systemic lupus erythematosus (SLE) is a complex, multifactor autoimmune disease. The studies on aetiopathogenesis of autoimmune diseases focus on the impact the genetically conditioned impairment of xenobiotic metabolism may exert. The knowledge of oxidation polymorphism in the course of SLE may be helpful in choosing more efficient and safer therapy. We determined whether there was an association between susceptibility to SLE and particularly to CYP2D6 genotypes.

Material and methods

The study was carried out in 60 patients with SLE and 129 healthy volunteers and all the subjects were of Polish origin. The samples were analysed for two major defective alles for CYP2D6 – CYP2D6*3 and CYP2D6*4 and one wild -type allele CYP2D6*1-by the polymerase chain reaction fragment length polymorphism (PCR-RFLP) metod with DNA extracted from peripheral blood.

Results

No statistically significant differences in the incidence of CYP2D6 genotypes between the studied groups were found (p = 0.615). Risk (OR) of SLE development was 1.03 for the carriers of CYP2D6*3 allele and 1.48 for the subjects with CYP2D6*4 allele; but it was not statistically significant.

Conclusions

Increased occurrence of mutant alleles of the CYP2D6 gene in SLE patients and the calculated OR values could suggest the effect of these mutations on increased SLE development.     

Multiplex family-based study in systemic lupus erythematosus: association between the R620W polymorphism of PTPN22 and the FcgammaRIIa (CD32A) R131 allele

A functional polymorphism in PTPN22, a gene encoding a phosphatase involved in T-cell signaling, has been associated with autoimmunity. We checked for the prevalence of the PTPN22 R620W polymorphism in multiplex families affected with systemic lupus erythematosus (SLE) and other autoimmune diseases. Its association with other polymorphisms in mannose binding lectin (MBL) and FcgammaRIIa (CD32A) genes was also studied. Deoxyribonucleic acid samples were obtained from 233 Spanish individuals who belonged to 21 families in which at least two members had been diagnosed with some autoimmune disease, mainly SLE. A healthy control population was also included (n= 129). Genotyping for the R620W single-nucleotide polymorphism (SNP) was performed by restriction fragment length polymorphism analysis of polymerase chain reaction products. Allele frequency for the T allele was slightly higher in the families with autoimmune disease, especially when considering the affected individuals (0.094 vs 0.062). Actually, 18.8% affected family members vs 11.6% controls had the polymorphism (P= 0.179). Nineteen percent of affected individuals had both the PTPN22 T and the CD32A R131 alleles, whereas only 8.5% unaffected relatives had both susceptibility alleles simultaneously [P= 0.031, odds ratios 2.508 (95% confidence interval 1.066-5.896)]. The tendency toward finding the T allele more frequently in members affected with some particular autoimmune disorder suggests that this SNP may confer susceptibility to autoimmunity. The fact that more affected than unaffected relatives carried both the T and the R131 alleles simultaneously leads us to think about the existence of a combinatorial effect between genes that could help define individuals prone to autoimmune diseases.     

系统性红斑狼疮遗传学研究进展

系统性红斑狼疮（systemic lupus erythematosus,SLE)通常被认为是自身免疫疾病的原型，遗传因素在疾病的发生中起重要作用。对狼疮鼠模型的研究已发现约30个基因位点与疾病产生有关，不同位点影响发病的不同环节。人类基因组研究则50个左右基因位点与SLE有关，其中1q23-24,1q41-42,2q37,4p16-15.2,6p21-11及16q13为6个显著相关区域，对特定患者，多个位点不同基因的组合可导致疾病表型的多样性。近期对候选基因的研究进一步证实，遗传因素在决定疾病易感性及临床表型时起作用，不同群体中所涉及的基因或其表达强度均有差异。     

Tumor necrosis factor-alpha single nucleotide polymorphisms in juvenile systemic lupus erythematosus

BackgroundJuvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disorder of unknown origin. Given the importance of the contribution of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), towards the pathogenesis of JSLE, this study was performed to assess TNFA gene polymorphisms in a case-control study.MethodsFifty nine patients with JSLE were enrolled in this study as case group and compared with healthy control subjects. The frequency of alleles, genotypes, and haplotypes of TNFA single-nucleotide polymorphisms (SNPs) at positions −308 and −238 were evaluated, using polymerase chain reaction with sequence-specific primers method.ResultsThe G allele at position −238 in TNFA promoter region was significantly more frequent in patients with JSLE than in the healthy controls (P value < 0.001), while the frequency of A allele at the same position was significantly lower than controls. Furthermore, a significant positive association for G/G genotype at the same position was detected in patients’ group compared with control subjects (P value < 0.001). The GA haplotype of TNFA (positions −308, −238) was significantly less frequent in case group than in controls (P value < 0.001), while GG was the most frequent haplotype for TNFA in the patient group, compared to controls (P value < 0.01).ConclusionsPro-inflammatory cytokine gene polymorphisms may influence susceptibility to JSLE. Particular TNFA gene variants are associated with JSLE and could be used as a genetic marker for susceptibility to JSLE.     

广西人群S100B基因多态性与系统性红斑狼疮的相关性研究

目的:探讨S100B基因rs9984765、rs2839356和rs2186358遗传多态性与系统性红斑狼疮(SLE)的相关性。方法:选取313例SLE患者作为病例组,年龄和性别匹配的396例正常人作为对照组,采用单碱基延伸PCR技术(SBE-PCR)和DNA测序法对S100B基因3个位点进行基因分型检测。结果:rs9984765和rs2186358位点的基因型和等位基因频率在SLE患者组和对照组间分布差异均无统计学显著性,而rs2839356位点的C等位基因在两组间比较差异有统计学意义(P=0. 040)。进一步分析rs2839356位点的等位基因与SLE患者临床表现的关系,发现rs2839356位点的C等位基因在伴有神经系统病变的SLE患者中高于不伴有神经系统病变的SLE患者(P=0. 023)。结论:在广西人群中,S100B基因rs9984765和rs2186358位点的基因多态性可能与SLE的遗传易感性无关,而携带rs2839356的C等位基因可能具有增加SLE及其并发神经系统病变的发病风险。     

Complement receptor 1 (CR1) on erythrocytes of patients with systemic lupus erythematosus

Ninety-five (85%) of the 112 Japanese patients with systemic lupus erythematosus (SLE) were negative for the complement receptor 1 (CR1) activities on erythrocytes, while 770 (91%) of the 847 normal subjects were positive for CR1, as determined by immune-adherence hemagglutination. Pedigree analyses of the normal population suggested that the phenotype of negative CR1 was determined by a autosomal recessive gene. Among 112 SLE patients, 73 (65%) showed persistently negative CR1 during remission for over 26 months of follow-up, although the CR1 levels did vary with the disease activity in 22 SLE patients. These results show that the relative risk for developing SLE in persons with negative CR1 is 19. CR1 activity appears to be an important genetic factor related the development of SLE.     

Inflammasome polymorphisms in juvenile systemic lupus erythematosus

Abstract

Inflammasome is the cytoplasmic complex responsible for pro-IL1?β cleavage and secretion of IL-1β. Recently our group reported the first association between polymorphisms in the inflammasome receptor NLRP1 and adult-onset systemic lupus erythematosus (SLE) “di per se” and especially in SLE-associated renal disease, suggesting the involvement of NLRP1-inflammasome in the immune dysregulation characteristic of SLE patients. Considering that juvenile-onset SLE (JSLE) is more severe than adult SLE, and that the genetic background plays a major role in the early development of autoimmune diseases, we analysed selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, IL1B, TNFAIP3) of children and adolescents with JSLE (n?=?90) and in healthy controls (n?=?144). A single polymorphism in IL1B, and not NLRP1, gene resulted in association with JSLE, suggesting that IL-1?β is involved in the pathogenesis of SLE, but different genes could play specific role in adult- or early-onset disease.     

NZM2328: a new mouse model of systemic lupus erythematosus with unique genetic susceptibility loci

Among NZB/W-derived New Zealand mixed (NZM) strains, only NZM/Aeg2410 (NZM2410) has been well characterized. In contrast to NZM2410, NZM2328 mice develop autoantibodies and acute and severe chronic glomerulonephritis (GN) with female predominance similarly to NZB/WF1 and humans with systemic lupus erythematosus (SLE). Chronic GN with glomerular sclerosis and tubular atrophy but not acute GN was correlated with severe proteinuria. In a backcross analysis of (NZM2328 X C57L/J) F1 X NZM2328, four SLE susceptibility genomic intervals were identified. One of them (Cgnz1) is on the telomeric end of chromosome 1 and close to Sle1. It was significantly linked to chronic GN. A locus (Agnz1) distinct from Cgnz1 on this interval was suggestively linked to acute GN. Two genetic intervals on chromosome 17 were also suggestively linked to acute GN, one of which is the H-2-Tnf complex, while the other (Agnz2) is on the distal end of the chromosome. A single locus (Adaz1) identified in the midregion of chromosome 4 in NZM2328 mice was suggestively linked to plasma levels of IgG anti-dsDNA autoantibodies. These results differ significantly from those in the backcross analysis of (NZM2410 X C57BL/6)F1 X NZM2410 by other investigators. They support the concept that different sets of genes are involved in acute and chronic GN. The genomic differences between the NZM strains and between C57L/J and C57BL/6 account for the differences between our analysis and that on NZM 2410. These results provide evidence for the importance of background genes on the expression of SLE, with implications for genetic studies of human SLE.     

Association of killer cell immunoglobulin-like receptor and human leucocyte antigen-Cw gene combinations with systemic lupus erythematosus

Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to human leucocyte antigen (HLA) class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune diseases. The present study aimed to investigate whether the combinations of KIR genes and HLA-Cw ligands associate with the susceptibility of systemic lupus erythematosus (SLE). Polymerase chain reaction using sequence-specific primers was used to determine the genotypes of KIR genes and HLA-Cw alleles. We found that the frequencies of HLA-Cw07 were statistically significantly higher in the patient group than those in the control group (P = 0·009). KIR2DS1⁺HLA⁻Cw^Lys was more common in subjects with SLE compared to control subjects (P = 0·015). In addition, the frequency of KIR2DS1 was increased in SLE when KIR2DL1/HLA-Cw are absent, and the difference was significant (P = 0·001). KIR genotype and HLA ligand interaction may potentially influence the threshold for NK (and/or T) cell activation mediated through activating receptors, thereby contributing to the pathogenesis of SLE.     

Association of apoptosis-related microsatellite polymorphisms on chromosome 1q in Taiwanese systemic lupus erythematosus patients

Apoptosis is important in the pathogenesis of systemic lupus erythematosus (SLE). Several genome-wide scan studies have suggested chromosome 1q as a genetic susceptibility locus for SLE. This study investigated the association of apoptosis-related genes on chromosome 1q, Fas ligand (FasL), interleukin (IL)-10 and poly(ADP-ribose) polymerase (PARP), promoter microsatellite multi-allelic polymorphisms with SLE susceptibility and clinical characteristics in Taiwan. This study recruited 237 SLE patients and 304 healthy controls. FasL, IL-10 and PARP promoter microsatellite polymorphisms were genotyped employing gene scan. IL-10, located on 1q31-32, emerged as a significant susceptibility gene locus in Taiwanese SLE (T4 statistic = 0.01). IL-10 CA21 allele was the most common allele of 15 identified in Taiwanese, displaying skewed distribution of susceptibility in Taiwanese SLE patients. Conversely, the IL-10 CA20 allele showed a protective effect of SLE susceptibility. Additionally, the IL-10 CA26 allele displayed a negative significant association with ascites and IL-10 CA25 allele increased the occurrence of the anti-cardiolipin IgM antibody. This study identified five alleles of FasL and nine alleles of PARP of microsatellite polymorphisms in Taiwanese patients. FasL and PARP alleles displayed no skewing distribution between Taiwanese SLE patients and controls. However, FasL GT15 and PARP CA17 allele demonstrated a high discoid rash presentation (T4 statistic 0.01 and 0.03, respectively) and PARP CA12 allele displayed a significant association with anti-cardiolipin IgM antibody production (T4 statistic 0.02). IL-10, FasL and PARP microsatellite polymorphisms exhibited significant associations with SLE susceptibility and/or clinical characteristics in Taiwanese patients. Thus, SLE is a complex and multiple genetics determined autoimmune disease. Chromosome 1q23-42 is an important genetic locus for further SLE subphenotype susceptibility study.     

Genetic studies on systemic lupus erythematosus in East Asia point to population differences in disease susceptibility

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with extreme clinical heterogeneity and significant differences between populations. East Asian populations are known to have higher prevalence and more severe clinical manifestations for SLE than Europeans. The difference could be the result of genetic and environmental factors, and the interactions between them. Thus, identifying genetic associations from diverse populations provides an opportunity to better understand the genetic architecture of this heterogeneous disease. It is also necessary to elucidate population differences and to apply the findings in future stratified treatment of the disease, with ethnicity likely a major factor to consider. Indeed, it has shown that there are significant differences between East Asians and European populations in several genetic loci for SLE. Genetic studies on SLE are very active in East Asian countries and there have been close collaborations among scientists in this region. Here, we document some work done in this region on SLE genetic research and discuss the aspect of population differences.     

Association of interleukin 22 gene polymorphisms and serum IL‐22 level with risk of systemic lupus erythematosus in a Chinese population

The aim of this study was to investigate the association between the single‐nucleotide polymorphisms (SNPs) of the interleukin 22 (IL‐22) gene and systemic lupus erythematosus (SLE) in a Chinese population. Three IL‐22 SNPs (rs2227485, rs2227513 and rs2227491) were genotyped using SNaPshot SNP genotyping assays and identified by sequencing in 314 SLE patients and 411 healthy controls. The IL‐22 level of serum was assessed by enzyme‐linked immunosorbent assay (ELISA) kits. Data were analysed by spss version 17.0 software. We found that rs2227513 was associated with an increased risk of SLE [AG versus AA: adjusted odds ratio (aOR) = 2·24, 95% confidence interval (CI) = 1·22–4·12, P = 0·010; G versus· A: adjusted OR = 2·18, 95% CI = 1·20‐3·97, P = 0·011]. Further analysis in patients with SLE showed that the AG genotype and G allele were associated with an increased risk of renal disorder in SLE (G versus A: aOR = 3·09, 95% CI = 1·30–7·33, P = 0·011; AG versus· AA: aOR = 3·25, 95% CI = 1·35–7·85, P = 0·009). In addition, the concentration of IL‐22 was significantly lower in the rs2227513 AG genotype compared with AA genotype (P = 0·028). These results suggest that rs2227513 polymorphism might contribute to SLE susceptibility, probably by decreasing the expression of IL‐22.