No association between interleukin 23 receptor gene polymorphisms and systemic lupus erythematosus

The objective of this study was to elucidate whether polymorphisms of the interleukin 23 receptor gene (IL23R) are associated with susceptibility to systemic lupus erythematosus (SLE) in a Korean population. We recruited 602 SLE patients and 991 healthy controls. Seven single nucleotide polymorphisms (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032, and rs1495965) were selected for genotyping among previously reported variants used in a genome-wide association study of inflammatory bowel disease. Polymorphic sites were genotyped using the TaqMan assay. The genotype distributions of IL23R polymorphisms and haplotypes were compared between the SLE patients and healthy controls using multiple logistic regression models. None of the IL23R genetic variants differed significantly between SLE patients and healthy controls, which suggests that IL23R polymorphisms play no role in the susceptibility to SLE in the Korean population.     

Interleukin-1 receptor antagonist gene polymorphism in chinese patients with systemic lupus erythematosus

The purpose of this study was to determine whether IL-1 receptor antagonist (IL-1Ra) gene polymorphism is a marker of susceptibility to or severity of systemic lupus erythematosus (SLE) in Chinese patients. The study included 52 Chinese patients with SLE. One hundred and three unrelated, healthy individuals living in central Taiwan served as controls. From genomic DNA, the polymorphism of the gene for IL-1Ra was typed. Allelic frequencies and carriage rates were compared between SLE patients and controls. The relationship between allelic frequencies and clinical manifestations of SLE was evaluated. We found an increased frequency of IL1RN*2 in the SLE patients compared to normal controls (χ²= 4.15, P<0.05), with an odds ratio (of allele frequency) of 2.63 (95% confidence interval 1.00–6.96). The carriage rate of IL1RN*2 was also higher in the SLE patients (6.8% in the controls vs. 17.3% in the SLE patients). We observed increased frequencies of malar rash and photosensitivity among patients with IL1RN*2 (77.8%) compared to patients without the allele (48.8%). However, this difference did not reach statistical significance (χ² = 2.51, P= 0.11). This study indicated that the frequency of IL1RN*2 is higher in Chinese SLE patients than in Chinese normal controls in Taiwan. However, there was no association between the frequency of IL1RN*2 and clinical manifestations. Received: 4 May 2001 / Accepted: 17 November 2001     

系统性红斑狼疮患者脱氧核糖核酸酶1基因多态性研究

目的：探讨脱氧核糖核酸酶1（DNASE1）基因单核苷酸多态性（SNP）与中国人系统性红斑狼疮（SLE）相关性。方法：验证文献报道的DNASE1基因3′端4个SNP，选取杂合度较高者对312个中国人群SLE家系以TaqManMGB等位基因识别技术在ABI7900HT序列测定仪上进行SNP基因分型，数据以SDS2．0软件收集，Genehunter进行统计处理并构建SNP单倍型。结果：中国人群中，DNASE1SNP3398，3737杂合度均接近0．5，4184亦有一定的杂合度。3398与3737的C－G单倍型优先传递给患病子代，3398、3737，4184的单位型C－G－G优先传递给患病子代（P＜0．05）。结论：在SLE患者中存在特定的SNP单倍型，部分SLE患者的发病与DNASE1基因相关联。     

白介素-23受体基因多态性与Graves病相关性研究

目的探讨白介素-23受体(IL-23R)基因rs2201841和rs10889677位点的遗传多态性和汉族人群Graves病易感性的关系。方法采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,检测286例Graves病患者和291名正常对照者IL-23R基因rs2201841和rs10889677两个位点的基因情况,分析其基因型和基因频率与Graves病的关系。结果 IL-23R基因rs2201841和rs10889677位点等位基因和基因型频率分布比较Graves病组和正常对照组间差异均无统计学意义(P>0.05),且这两个位点多态性与发病的年龄及性别均无相关性。结论 IL-23R基因rs2201841和rs10889677两个位点多态性情况,可能不是中国南方汉族人群Graves病发病的危险因素。     

A polymorphism within IL21R confers risk for systemic lupus erythematosus

Objective

Interleukin‐21 (IL‐21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL‐21 receptor (IL‐21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL‐21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single‐nucleotide polymorphisms (SNPs) within IL21R and SLE.

Methods

We genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European‐derived cohort and a Hispanic cohort) and in ethnically matched healthy controls.

Results

We identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta‐analysis odds ratio 1.16 [95% confidence interval 1.08–1.25], P = 1.0 × 10⁻⁴).

Conclusion

Our findings indicate that IL21R is a novel susceptibility gene for SLE.

     

Mannose-binding protein gene polymorphism in systemic lupus erythematosus

Objective. To determine whether an allelic form of mannose-binding protein (MBP) incapable of activating complement is associated with susceptibility to systemic lupus erythematosus (SLE). Methods. MBP allele frequencies were determined by amplification refractory mutation system–polymerase chain reaction in 102 white SLE patients and 136 controls. Results. The MBP allele that is unable to activate complement was present in 42 SLE patients (41%) and in 41 controls (30%) (P = 0.08, odds ratio [OR] = 1.6, 95% confidence interval [95% CI] 1.0–2.8). The gene frequency of this allele was 0.25 in SLE patients and 0.19 in controls (P = 0.08, OR = 1.5, 95% CI 1.0–2.3). Conclusion. Our results suggest that this allele of the MBP gene represents a minor risk factor for SLE.     

Transforming growth factor-12 polymorphism and systemic lupus erythematosus

OBJECTIVE: To determine whether transforming growth factor-beta2 (TGF-beta2) gene polymorphism is associated with systemic lupus erythematosus (SLE) susceptibility. TGF-beta is a multifunctional family of cytokines important in tissue repair, inflammation and immunoregulation. SLE is thought to be a T cell dependent autoimmune disorder with T cell dysfunction. Due to its known suppressive effects on interleukin 2 dependent T cell growth, TGF-beta2 is considered to be a candidate SLE susceptibility gene. Furthermore, SLE has been linked with a region to which the TGF-beta2 gene has been mapped. METHODS: Association studies were performed in 3 case-control populations, from Spain. Turkey, and UK, using a TGF-beta2 5'-untranslated region (5'-UTR) 4 base pair (bp) insertion polymorphism. Genotyping was performed using fluorescent labeled polymerase chain reaction product sizing. Results. No significant differences were detected in TGF-beta2 5'-UTR polymorphism allele frequencies between SLE patients and matched controls in the 3 populations studied. CONCLUSION. The 4 bp insertion polymorphism within the TGF-beta2 gene does not appear to be associated with SLE. However, this does not rule out the possible involvement of TGF-beta2 in the disease pathogenesis.     

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

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

维生素D受体起始密码子基因多态性与系统性红斑狼疮相关性研究

目的 检测维生素D受体(VDR)基因多态性在系统性红斑狼疮(SLE)患者中的分布,探讨其与SLE发病的相关性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测VDR起始密码子(FokI)多态性位点和基因型在271例SLE患者和130名健康对照组中的分布情况.采用χ2检验和方差分析进行统计学处理.结果 SLE患者及健康对照组VDR FokI多态性基因型和等位基因分布均不处于Hardy-Weinberg平衡(SLE组χ2=7.883,P=0.019;健康对照组:χ2=7.288,P=0.026).VDR FokI多态性等位基因F和f的分布频率在健康对照组分别为48.8%和51.2%,在SLE组分别为60.9%(χ2=10.39,P=0.001)和39.1%(χ2=10.39,P=0.001);F等位基因个体发生SLE的比值比(OR)为1.630(95%CI=1.210～1.1%,χ2=10.39,P=0.001).基因型FF、Ff和ff分布频率在健康对照组中分别为25.4%、46.9%和27.7%,在SLE组中分别为42.8%(χ2=11.417,P=0.001)、36.2(χ2=4.251,P=0.039)和21.0%(χ2=2.187,P=0.139);FF和Ff基因型个体发生SLE的OR分别为2.200(95%CI=1.385～3.493,χ2=11.417,P=0.001)和0.641(95%C1=0.419～0.979,χ2=4.251,P=0.039).进一步分析发现,不同VDR FokI多态性基因型SLE患者之间疾病活动性积分(SLEDAI)差异无统计学意义(P=0.382).但与FF和ff基因型SLE患者对照,Ff基因型SLE患者中浆膜炎的发生率更高(P=0.001),而且具有更高阳性率的抗双链DNA(dsDNA)抗体(P=0.001)、抗Sm抗体(P=0.047)和抗组蛋白抗体(P=0.001),但皮疹发生率较低(P=0.005).结论 VDR FokI多态性位点F等位基因和F/F及F/f基因型与SLE发病易感性有关,而且F/f杂合子患者更容易发生浆膜炎和产生抗dsDNA抗体、抗Sm抗体和抗组蛋白抗体.     

Epidermal growth factor receptor (EGFR) gene Bsr I polymorphism is associated with systemic lupus erythematosus

The purpose of this study was to determine if epidermal growth factor receptor (EGFR) gene polymorphism was a marker of susceptibility to or severity of Chinese patients with systemic lupus erythematosus (SLE) in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Polymorphisms of the EGFR Bsr I gene were typed from genomic DNA. The genotypes, allelic frequencies and carriage rates were compared between SLE patients and control subjects. The relationship between allelic frequencies and clinical manifestations of SLE was evaluated. For the genotype of EGFR gene Bsr I polymorphism, there was statistically significant differences between the SLE and control groups (chi-squared test, P = 0.009, chi2 = 9.21). In addition, there was significant association between the two groups in allelic frequency of the T allele (P = 0.02, chi2 = 5.27). However, we did not detect any association between EGFR genotype and clinical or laboratory profiles in SLE patients. The results suggest that the EGFR gene Bsr I polymorphism is related to SLE.     

Contribution of toll-like receptor 9 gene single-nucleotide polymorphism to systemic lupus erythematosus

There are several studies on the association of TLR9 polymorphisms with systemic lupus erythematosus (SLE) in different ethnicities; however, the results are inconsistent. Therefore, we studied the distribution of the TLR9 C > T (rs352140) polymorphism in patients with SLE (n = 254) and controls (n = 521) in a Polish population. We did not observe significant differences in the prevalence of the TLR9 C > T genotype and alleles between patients with SLE and controls. However, we found a contribution of the T/T and T/C genotypes to renal [OR = 2.949 (95 % CI = 1.523–5.711, p = 0.001), (p _corr = 0.017)] and immunologic disorders [OR = 2.938 (95 % CI 1.500–5.755, p = 0.0012), (p _corr = 0.0204)] in SLE patients. Moreover, we observed a significant association between the TLR9 T/T and T/C genotypes and the presence of anti-dsDNA Ab [OR = 3.682 (1.647–8.230, p = 0.001), (p _corr = 0.017)]. Our studies suggest that the TLR9 C > T (rs352140) polymorphism might contribute to renal and immunologic disorders and to the presence of anti-dsDNA Ab.     

APRIL polymorphism and systemic lupus erythematosus (SLE) susceptibility

OBJECTIVE: Two novel non-synonymous polymorphisms of the APRIL gene, codon 67 (rs11552708) and 96 (rs3803800), were recently identified and tested for disease association. The 67G allele was reported to be associated with systemic lupus erythematosus (SLE) in a Japanese population. The aim of the study is to investigate whether the APRIL polymorphism associated with susceptibility to SLE in a Japanese population is associated with the susceptibility to SLE in other ethnic groups. METHODS: Three hundred and forty-eight SLE patients (204 European-American, 103 African-American and 41 Hispanic) and 345 ethnicity-matched controls (201 European-American, 104 African-American and 40 Hispanic) were included from the Lupus Multiplex Registry and Repository (LMRR) and evaluated for genetic association. The APRIL codon 67 and codon 96 were genotyped by a 3-base extension method. Statistical evaluations were performed using both chi-square and logistic regression analysis. RESULTS: Both the single-nucleotide polymorphisms (SNPs) were in Hardy-Weinberg equilibrium in cases and controls within each ethnic group. The APRIL codon 67 was significantly associated with SLE risk under the dominant model adjusted by ethnicity (odds ratio, 95% confidence interval and P-values were 1.45 and 1.02-2.06 and 0.036, respectively). Race-specific analysis also showed a trend for association in African-American and Hispanic SLE subjects. CONCLUSION The APRIL codon G67R polymorphism associated with SLE in a Japanese population may also be associated with SLE in other populations.     

Interleukin–1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus

Objective. We have previously described associations between an allele of the interleukin–1 receptor antagonist gene (IL1RN) and several inflammatory diseases. In this study we tested the IL1RN gene as a possible marker in patients with systemic lupus erythematosus (SLE). Methods. Eighty–one SLE patients and 261 ethnically matched control subjects were genotyped by polymerase chain reaction. Results. We found an increase in both frequency and carriage rate of IL1RN*2 in the SLE group. This association strengthened with extensive disease and particularly with the presence of photosensitivity and discoid skin lesions. Conclusion. We describe a novel association between IL1RN*2 and SLE. Carriage of the allele seems to influence severity rather than susceptibility to SLE. We postulate that the association of this polymorphism with disease severity is a widespread feature of common inflammatory and autoimmune diseases.     

Clinical significance of vitamin D deficiency and receptor gene polymorphism in systemic lupus erythematosus patients

Introduction

The vitamin D receptor (VDR) gene is a candidate for susceptibility to autoimmune disorders.

中国汉族人群系统性红斑狼疮患者信号传导和转录激活子4基因多态性研究

目的 探讨信号传导和转录激活子4(STAT4)基因多态性与中国汉族人群系统性红斑狼疮(SLE)的相关性.方法 运用焦磷酸测序的方法对SLE患者与健康对照组DNA中存在的3个单核苷酸多态性位点进行分型,并作统计学分析.结果 STAT4基因的3个单核苷酸多态性(SNP)及其构成的单倍型在患者与健康对照组间差异均有统计学意义[rs11889341:P=012 02,0R(95%CI)=1.22(1.044～1.424);m7574865:P=0.003 454,OR(95%CI)=1.25(1.076～1.451);rs8179673:P=0.004 275,OR(95%CI)=1.274(1.079～1.505)].结论 STAT4基因上ra11889341、rs7574865和rs8179673与中国汉族人群SLE的发病有关联,且STAT4是-个多种族均存在的SLE相关基因.