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聚(ADP-核糖)聚合酶(PARP)多态性与韩国人群类风湿关节炎之间缺乏关联。

Lack of association between poly(ADP-ribose) polymerase (PARP) polymorphisms and rheumatoid arthritis in a Korean population.

机构信息

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 17 Haengdang-Dong, Seongdong-Gu, Seoul 133-792, South Korea.

出版信息

Rheumatol Int. 2012 Jan;32(1):91-6. doi: 10.1007/s00296-010-1589-9. Epub 2010 Jul 28.

Abstract

Several studies have investigated the roles of genetic polymorphisms in rheumatoid arthritis (RA). Some of these studies reported that polymorphisms of poly(ADP-ribose) polymerase 1 gene (PARP-1) are linked to rheumatoid arthritis. Poly(ADP-ribose) polymerase is an enzyme involved in DNA repair, genomic stability, apoptosis, gene transcription, proliferation, and autoimmunity. To determine whether genetic polymorphisms of PARP-1 are related to rheumatoid arthritis in a Korean population, six single nucleotide polymorphisms (SNPs), which were selected based on LDs and minor allele frequency (MAF > 0.05) in our previous study, were genotyped in 1,202 patients with rheumatoid arthritis and 979 unrelated healthy controls. As a result, no significant association between the susceptibility to rheumatoid arthritis and PAPR-1 polymorphisms was found. However, in further analysis depending on the radiological severity of rheumatoid arthritis, one PARP-1 polymorphism, rs1805413 (OR = 0.11; 95% CI = 0.02-0.55; P = 0.007; P (corr) = 0.04), and one haplotype (ht6, OR = 0.11; 95% CI = 0.02-0.55; P = 0.007; P (corr) = 0.04) were significantly associated with the radiological severity risk of RA in a recessive model. In addition, a recessive model revealed a correlation between one RA haplotype (ht4) and anti-CCP antibody negativity (OR 0.24, 95% CI 0.10-0.63, P = 0.003; P (corr) = 0.02). Despite a possible association between PARP-1 and the radiological severity of RA, this study found no statistical association between PARP-1 polymorphisms and the susceptibility to rheumatoid arthritis in a Korean population.

摘要

已有多项研究探讨了遗传多态性在类风湿关节炎(RA)中的作用。其中一些研究报告称,多聚(ADP-核糖)聚合酶 1 基因(PARP-1)的多态性与类风湿关节炎有关。多聚(ADP-核糖)聚合酶是一种参与 DNA 修复、基因组稳定性、细胞凋亡、基因转录、增殖和自身免疫的酶。为了确定 PARP-1 的遗传多态性是否与韩国人群中的类风湿关节炎有关,我们根据先前研究中的 LD 和次要等位基因频率(MAF>0.05)选择了 6 个单核苷酸多态性(SNP),并对 1202 名类风湿关节炎患者和 979 名无关健康对照者进行了基因分型。结果发现,PARP-1 多态性与类风湿关节炎的易感性之间没有显著关联。然而,在进一步根据类风湿关节炎的放射学严重程度进行分析时,发现 PARP-1 多态性 rs1805413(OR=0.11;95%CI=0.02-0.55;P=0.007;P(corr)=0.04)和一个单倍型(ht6,OR=0.11;95%CI=0.02-0.55;P=0.007;P(corr)=0.04)在隐性模型中与 RA 的放射学严重程度风险显著相关。此外,在隐性模型中发现一个 RA 单倍型(ht4)与抗 CCP 抗体阴性之间存在相关性(OR 0.24,95%CI 0.10-0.63,P=0.003;P(corr)=0.02)。尽管 PARP-1 与 RA 的放射学严重程度之间可能存在关联,但本研究在韩国人群中并未发现 PARP-1 多态性与类风湿关节炎易感性之间存在统计学关联。

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