Abstract
ObjectivesDendritic 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.MethodsWe 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.Results 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 (ORoverall = 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).ConclusionsOur 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.
Highlights
Rheumatoid arthritis (RA) is a common autoimmune disease, characterized by chronic inflammation and progressive destruction in the joints
Over 30 RA susceptibility loci have been identified [1] and the most important genetic factor for RA was found in a group of the human leukocyte antigen (HLA)-DRB1 alleles named as shared epitope (SE) [2]
The aim of this study was to investigate the possible association of Dendritic cell immunoreceptor (DCIR) polymorphisms with anti-citrullinated protein antibodies (ACPA)-positive and ACPA-negative RA in four independent Asian populations originated from China and Malaysia. Both single nucleotide polymorphisms (SNPs) rs2377422 and rs10840759 were in Hardy-Weinberg equilibrium (HWE) (P.0.05) in cases and controls of Han Chinese cohort, with the study power of 0.986 to detect the modest effect size with odds ratios (OR) = 1.40, and a fixed minor allele frequency of 40% for RA association
Summary
Rheumatoid arthritis (RA) is a common autoimmune disease, characterized by chronic inflammation and progressive destruction in the joints. The pathogenesis of RA remains poorly understood, it is widely accepted that genetic risk factors contribute significantly to RA development. Over 30 RA susceptibility loci have been identified [1] and the most important genetic factor for RA was found in a group of the human leukocyte antigen (HLA)-DRB1 alleles named as shared epitope (SE) [2]. The majority of RA susceptibility loci have been described as risk factors for anti-citrullinated protein antibodies (ACPA)-positive RA [2,3,4,5,6]. Direct comparison between disease subgroups revealed that different genetic association patterns existed between ACPA-positive and ACPA-negative RA, and little is known about the genetic contribution to ACPAnegative RA [7]. Expanding the genetic study population(s) is needed to validate the existing genetic risk factors, and to understand the implication of genetic heterogeneity among the populations in RA
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