Related Experiment Video
Updated: May 23, 2026
07:37
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Associations between six classical HLA loci and rheumatoid arthritis: a comprehensive analysis
S Mitsunaga1, Y Suzuki, M Kuwana
1Department of Molecular Life Sciences, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Tissue Antigens
|April 5, 2012
Summary
This study reveals that human leukocyte antigen (HLA) loci beyond DRB1, specifically DPB1, are significantly associated with rheumatoid arthritis (RA) risk and disease severity. Comprehensive analysis of multiple HLA loci is crucial for understanding RA
Area of Science:
- Immunogenetics
- Rheumatology
- Human Genetics
Background:
- The human leukocyte antigen (HLA) region is a major genetic contributor to rheumatoid arthritis (RA), accounting for one-third of genetic factors.
- Previous research has primarily focused on the HLA-DRB1 locus, with limited investigation into other HLA loci's association with RA.
- Understanding the genetic architecture of RA requires exploring the roles of multiple HLA loci beyond DRB1.
Purpose of the Study:
- To investigate the association between RA and alleles of six classical HLA loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) in a Japanese population.
- To determine if non-DRB1 HLA loci confer RA risk or protection independently of DRB1.
- To assess the association of specific HLA alleles and haplotypes with RA disease types and anti-cyclic citrullinated peptides (CCP) antibody status.
Main Methods:
- Genotyping of six HLA loci in 1659 Japanese individuals (622 RA cases and 1037 controls).
- Stratification of RA cases based on anti-CCP antibody status and disease type.
- Statistical analyses including Fisher's exact tests, odds ratios, trend tests, and haplotype estimation.
Main Results:
- No significant association was found between HLA loci and anti-CCP antibody-negative RA after Bonferroni correction.
- Several non-DRB1 HLA loci alleles showed significant association with anti-CCP antibody-positive RA.
- DPB1 alleles (DPB1*02:01, DPB1*04:01, DPB1*09:01) demonstrated independent risk or protective effects against RA, irrespective of DRB1.
- DPB1*02:01 was linked to a highly erosive RA phenotype.
- Haplotype analysis revealed significant associations for combinations including DRB1*04:05 and DQB1*04:01, with odds ratios ranging from 1.01 to 5.58.
- HLA-C*07:04 and HLA-B*15:18 showed associations comparable to HLA-DRB1*04:01 when on the same haplotype.
Conclusions:
- The study highlights the significant role of HLA loci beyond DRB1, particularly DPB1, in the genetic susceptibility to RA.
- Comprehensive analysis incorporating multiple HLA loci and their haplotypes provides a more complete understanding of HLA's genetic association with RA.
- These findings underscore the need to consider a broader spectrum of HLA genes in RA genetic research and potential therapeutic strategies.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22Rheumatic Heart Disease II: Clinical Manifestations and Diagnostic Studies
The key clinical manifestations of Rheumatic heart disease (RHD) include several distinct cardiac symptoms.Carditis, a hallmark of acute rheumatic fever, involves inflammation of the heart's endocardium, myocardium, and pericardium. Chronic RHD often results from recurrent episodes of carditis. Its symptoms include the following:Murmurs are caused by valvular damage, especially to the mitral and aortic valves. Mitral stenosis or regurgitation is common, with characteristic heart murmurs...