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土耳其类风湿性关节炎患者肿瘤坏死因子-α和白细胞介素-10基因启动子多态性

Tumor necrosis factor-alpha and interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients.

作者信息

Ates Omer, Hatemi Gulen, Hamuryudan Vedat, Topal-Sarikaya Aysegul

机构信息

Department of Molecular Biology and Genetics, Science Faculty, Istanbul University, 34118 Vezneciler, Istanbul, Turkey.

出版信息

Clin Rheumatol. 2008 Oct;27(10):1243-8. doi: 10.1007/s10067-008-0893-1. Epub 2008 Apr 22.

Abstract

Tumor necrosis factor and interleukin 10 have been implicated in the pathogenesis of rheumatoid arthritis (RA). Certain single-nucleotide polymorphisms (SNPs) within the promoter region of the IL-10 and TNF genes have been associated with altered levels of circulating IL10 and TNF. We aimed to explore the association of IL-10 and TNF-alpha polymorphisms in Turkish RA patients. We analyzed the association of TNF-alpha (-308G/A, -238G/A, -376G/A) and IL10 (-1082G/A, -819C/T, -592C/A) polymorphisms in 98 Turkish patients with rheumatoid arthritis and 122 healthy subjects using ARMS-PCR. The correlation of these findings with RF positivity and erosive disease in RA patients was also sought. A significant association was found between having RA and -1082 G allele (p=0.008; OR=1.44, 95% CI 1.11-1.86). There was no association between RA and -819C/T polymorphism. Significant differences were observed in IL10 GCC and ACC haplotypes distribution between RA and control subjects (p=0.006; OR=1.46, 95% CI 1.13-1.89 and p=0.011; OR=1.43, 95% CI 1.09-1.88, respectively). No statistically significant association was found between TNF-alpha 308G/A, -238G/A, -376G/A polymorphisms and RA. No significant association was found between RF positivity and erosive disease and TNF-alpha, IL10 gene polymorphisms. In addition, when combined genotypes were analyzed, no significant difference was found between RA patients and healthy controls. Our findings suggest that IL-10 1082 G/A polymorphism or GCC, ACC haplotypes may be associated with RA in Turkish patients.

摘要

肿瘤坏死因子和白细胞介素10与类风湿关节炎(RA)的发病机制有关。白细胞介素10(IL-10)和肿瘤坏死因子(TNF)基因启动子区域内的某些单核苷酸多态性(SNP)与循环中IL-10和TNF水平的改变有关。我们旨在探讨土耳其RA患者中IL-10和TNF-α多态性之间的关联。我们采用扩增阻滞突变系统聚合酶链反应(ARMS-PCR)分析了98例土耳其类风湿关节炎患者和122名健康对照者中TNF-α(-308G/A、-238G/A、-376G/A)和IL-10(-1082G/A、-819C/T、-592C/A)多态性。还研究了这些发现与RA患者中类风湿因子(RF)阳性及侵蚀性疾病的相关性。发现患RA与-1082 G等位基因之间存在显著关联(p=0.008;比值比[OR]=1.44,95%置信区间[CI] 1.11-1.86)。RA与-819C/T多态性之间无关联。在RA患者和对照者之间观察到IL-10 GCC和ACC单倍型分布存在显著差异(分别为p=0.006;OR=1.46,95%CI 1.13-1.89和p=0.011;OR=1.43,95%CI 1.09-1.88)。未发现TNF-α 308G/A、-238G/A、-376G/A多态性与RA之间存在统计学显著关联。未发现RF阳性及侵蚀性疾病与TNF-α、IL-10基因多态性之间存在显著关联。此外,分析合并基因型时,RA患者与健康对照者之间未发现显著差异。我们的研究结果表明,IL-10 1082 G/A多态性或GCC、ACC单倍型可能与土耳其患者的RA有关。

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