Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2012 Sep;125(17):3115-9.
Macrophage-inducible C-type lectin (MINCLE) is an important member of C-type lectin superfamily, which has been shown evidence for susceptibility to arthritis in animal models. We aimed to investigate the possible association of MINCLE with rheumatoid arthritis (RA) susceptibility in Chinese Han population.
Haplotypes from HapMap database (Chinese Han Beijing, CHB) were used to select tag-single nucleotide polymorphism (SNP) (r(2) = 0.8) residing in MINCLE gene. A total of 563 patients with RA and 404 healthy controls were TagMan genotyped for SNP rs10841845. Association analyses were performed on the whole data set and on RA subsets based on gender difference and the status of anti-cyclic citrullinated peptide (anti-CCP) antibody in RA patients. Association statistics were calculated by age and sex adjusted logistic regression.
Overall, MINCLE SNP rs10841845 was not associated with susceptibility to RA. However, following anti-CCP stratification, rs10841845 GG genotypes conferred a significantly protective effects against anti-CCP-positive RA (OR 0.65, 95%CI 0.430 - 0.995, P = 0.048). Following gender stratification, SNP rs10841845 G allele appeared to insert its RA protective effect only in male patients, both at allele level (G vs. A OR 0.66, 95%CI 0.46 - 0.93, P = 0.018) and at genotype level (GG vs. AA+AG, OR 0.429, 95%CI 0.20 - 0.95, P = 0.036). Notably, the male RA protective effect of rs10841845 G allele was only seen in anti-CCP-positive RA (G vs. A: OR 0.64, 95%CI 0.43 - 0.96, P = 0.029; GG vs. AA+AG: OR 0.375, 95%CI 0.14 - 0.94, P = 0.038). Furthermore, we observed a significant reduction of Disease Activity Score (DAS) 28 score (3.91 ± 0.70 vs. 5.66 ± 0.31, P = 0.022) and serum C-reactive protein levels (31.64 ± 24.13 vs. 91.80 ± 12.02, P = 0.012) in male anti-CCP-positive RA patients carrying rs10841845 GG genotype, compared with patients carrying AA+AG genotypes.
Our study provides the evidence for a gender specific association between MINCLE rs10841845 and RA susceptibility. The SNP rs10841845 G allele appears to have protective effect against anti-CCP-positive RA and confer reduced RA activity in men.
巨噬细胞诱导型 C 型凝集素（MINCLE）是 C 型凝集素超家族的重要成员，在动物模型中已被证明与关节炎易感性有关。我们旨在研究 MINCLE 与中国汉族人群类风湿关节炎（RA）易感性之间可能的关联。
使用 HapMap 数据库（中国汉族北京，CHB）中的单倍型选择标签单核苷酸多态性（SNP）（r²=0.8），这些 SNP 位于 MINCLE 基因内。对 563 名 RA 患者和 404 名健康对照者进行 TagMan 基因分型，以检测 SNP rs10841845。在全数据集和基于 RA 患者的性别差异和抗环瓜氨酸肽（抗-CCP）抗体状态的 RA 亚组中进行关联分析。使用年龄和性别调整的逻辑回归计算关联统计数据。
总体而言，MINCLE SNP rs10841845 与 RA 的易感性无关。然而，在抗-CCP 分层后，rs10841845 GG 基因型对抗-CCP 阳性 RA 具有显著的保护作用（OR 0.65，95%CI 0.430-0.995，P=0.048）。在性别分层后，SNP rs10841845 G 等位基因似乎仅在男性患者中表现出 RA 的保护作用，无论是在等位基因水平（G 对 A OR 0.66，95%CI 0.46-0.93，P=0.018）还是在基因型水平（GG 对 AA+AG，OR 0.429，95%CI 0.20-0.95，P=0.036）。值得注意的是，rs10841845 G 等位基因在男性抗-CCP 阳性 RA 中的保护作用仅在抗-CCP 阳性 RA 中可见（G 对 A：OR 0.64，95%CI 0.43-0.96，P=0.029；GG 对 AA+AG：OR 0.375，95%CI 0.14-0.94，P=0.038）。此外，我们观察到男性抗-CCP 阳性 RA 患者携带 rs10841845 GG 基因型的疾病活动评分（DAS）28 评分（3.91±0.70 对 5.66±0.31，P=0.022）和血清 C 反应蛋白水平（31.64±24.13 对 91.80±12.02，P=0.012）显著降低。
我们的研究为 MINCLE rs10841845 与 RA 易感性之间的性别特异性关联提供了证据。SNP rs10841845 G 等位基因似乎对抗-CCP 阳性 RA 具有保护作用，并在男性中降低 RA 活动度。
