WU Xin-yu, GUO Jian-ping,YIN Fang-rui, LU Xiao-lan, LI Ru, HE Jing, LIU Xu, LI Zhan-guo

Background  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.
Methods  Haplotypes from HapMap database (Chinese Han Beijing, CHB) were used to select tag-single nucleotide polymorphism (SNP) (r2=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.
Results  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.
Conclusions  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.