Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing, China.
PLoS One. 2012;7(7):e41228. doi: 10.1371/journal.pone.0041228. Epub 2012 Jul 19.
Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.
We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.
DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).
Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
树突状细胞免疫受体 (DCIR) 已被发现在啮齿动物自身免疫疾病的发展中起作用，并且 DCIR 多态性与瑞典白种人中抗瓜氨酸化蛋白抗体 (ACPA) 阴性类风湿关节炎 (RA) 相关。本研究旨在进一步探讨 DCIR 多态性是否也是来自中国和马来西亚的四个亚洲人群发生 RA 的危险因素。
我们在中国汉族人群（1193 例病例，1278 例对照）中对两个 DCIR SNPs rs2377422 和 rs10840759 进行了基因分型，以评估它们与 RA 的关联。随后，我们在三个独立的马来西亚华人队列（MY_Chinese，254 例病例，206 例对照）、马来人队列（MY_ Malay，515 例病例，986 例对照）和马来西亚印度人队列（MY_Indian，378 例病例，285 例对照）中进一步对 rs2377422 进行了基因分型，以寻求在不同种族群体中关联的确认。进行了荟萃分析，以评估 rs2377422 多态性对不同种族群体中 ACPA 阴性 RA 的发生的贡献。最后，我们进行了 rs2377422 多态性与 DCIR mRNA 表达水平的关联分析。
发现 DCIR rs2377422 与汉族的 ACPA 阴性 RA 显著相关（OR 1.92，95% CI 1.27-2.90，P=0.0020）。荟萃分析证实，DCIR rs2377422 是不同种族群体中 ACPA 阴性 RA 的危险因素（OR（整体）=1.17，95% CI 1.06-1.30，P=0.003）。SNP rs2377422 多态性与 DCIR mRNA 表达水平显著相关，即 RA 风险 CC 基因型的 DCIR 表达显著增加（P=0.0023，Kruskal-Wallis）。
我们的数据提供了 DCIR rs2377422 与非白种人群 RA 之间关联的证据，并证实了 DCIR 多态性对 RA 易感性的影响，特别是对 ACPA 阴性 RA 的影响。
