Interaction of HLA-DRB1*09:01 and*04:05 with Smoking Suggests Distinctive Mechanisms of Rheumatoid Arthritis Susceptibility Beyond the Shared Epitope
- Authors
- Bang, So-Young; Lee, Hye-Soon; Lee, Kyung Wha; Bae, Sang-Cheol
- Issue Date
- Jul-2013
- Publisher
- J RHEUMATOL PUBL CO
- Keywords
- RHEUMATOID ARTHRITIS; HLA-DRB1*09:01; SHARED EPITOPE; ANTICITRULLINATED PROTEIN AUTOANTIBODIES; SMOKING
- Citation
- JOURNAL OF RHEUMATOLOGY, v.40, no.7, pp.1054 - 1062
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF RHEUMATOLOGY
- Volume
- 40
- Number
- 7
- Start Page
- 1054
- End Page
- 1062
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/26694
- DOI
- 10.3899/jrheum.121280
- ISSN
- 0315-162X
- Abstract
- Objective. Although HLA-DRB1 shared epitope (SE) alleles and HLA-DRB1*09:01 have repeatedly been shown to be associated with susceptibility to rheumatoid arthritis (RA), the effect of each allele on levels of anticyclic citrullinated peptide autoantibodies (anti-CCP) and interaction with cigarette smoking in RA remains to be fully defined. We investigated whether HLA-DRB1 risk alleles influence anti-CCP levels and whether each allele interacts with smoking in anti-CCP-positive or -negative RA. Methods. All patients with RA (n = 1924) and controls (n = 1119) were Korean. The HLA-DRB1 4-digit genotyping was performed by standard PCR-sequencing based typing method. OR and biologic interactions as departures from additivity or multiplicity were analyzed by logistic regression. Results. SE alleles were significantly associated with increased anti-CCP levels. Conversely, HLA-DRB1*09:01 was associated with reduced levels, in both SE-positive and SE-negative patients. Each of SE alleles interacted significantly with smoking, whereas HLA-DRB1*09:01 did not. Interactions between the 2 most significant risk alleles, HLA-DRB1*04:05 and HLA-DRB1*09:01, (attributable proportion = 0.68, 95% CI 0.46-0.89, multiplicity p = 0.012) significantly increased RA susceptibility regardless of anti-CCP and smoking status. Smoking increased the risk for RA by significant interaction with the heterozygote HLA-DRB1*04:05/*09:01. Conclusion. HLA-DRB1*09:01 differs from SE alleles with regard to anti-CCP levels and interaction with smoking, suggesting a distinct mechanism of HLA-DRB1*09:01 in the pathogenesis of RA that may bypass anti-CCP formation. Also, a significant increase of the HLA-DRB1*04:05/*09:01 heterozygote in RA susceptibility may be attributable to the synergistic contribution of 2 different pathways in which 2 alleles participate independently.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 내과학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/26694)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.