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Interactions Between Amino Acid-Defined Major Histocompatibility Complex Class II Variants and Smoking in Seropositive Rheumatoid Arthritis

Title
Interactions Between Amino Acid-Defined Major Histocompatibility Complex Class II Variants and Smoking in Seropositive Rheumatoid Arthritis
Author
이혜순
Keywords
CITRULLINATED PEPTIDE ANTIBODY; GENE-ENVIRONMENT INTERACTION; SHARED EPITOPE ALLELES; GENOME-WIDE ASSOCIATION; CIGARETTE-SMOKING; FINE-SPECIFICITY; RISK; SUSCEPTIBILITY; HLA; PROTEINS
Issue Date
2015-10
Publisher
WILEY-BLACKWELL
Citation
ARTHRITIS & RHEUMATOLOGY, v. 67, NO 10, Page. 2611-2623
Abstract
Objective. To define the interaction between cigarette smoking and HLA polymorphisms in seropositive rheumatoid arthritis (RA), in the context of a recently identified amino acid-based HLA model for RA susceptibility. Methods. We imputed Immunochip data on HLA amino acids and classical alleles from 3 case-control studies (the Swedish Epidemiological Investigation of Rheumatoid Arthritis [EIRA] study [1,654 cases and 1,934 controls], the Nurses' Health Study [NHS] [229 cases and 360 controls], and the Korean RA Cohort Study [1,390 cases and 735 controls]#. We examined the interaction effects of heavy smoking #˃ 10 pack-years# and the genetic risk score #GRS# of multiple RA-associated amino acid positions #positions 11, 13, 71, and 74 in HLA-DR beta 1, position 9 in HLA-B, and position 9 in HLA-DP beta 1#, as well as the interaction effects of heavy smoking and the GRS of HLA-DR beta 1 4-amino acid haplotypes #assessed via attributable proportion due to interaction [AP] using the additive interaction model#. Results. Heavy smoking and all investigated HLA amino acid positions and haplotypes were associated with RA susceptibility in the 3 populations. In the interaction analysis, we found a significant deviation from the expected additive joint effect between heavy smoking and the HLA-DR beta 1 4-amino acid haplotype #AP 0.416, 0.467, and 0.796, in the EIRA, NHS, and Korean studies, respectively#. We further identified the key interacting variants as being located at HLA-DR beta 1 amino acid positions 11 and 13 but not at any of the other RA risk-associated amino acid positions. For residues in positions 11 and 13, there were similar patterns between RA risk effects and interaction effects. Conclusion. Our findings of significant gene-environment interaction effects indicate that a physical interaction between citrullinated autoantigens produced by smoking and HLA-DR molecules is characterized by the HLA-DR beta 1 4-amino acid haplotype, primarily by positions 11 and 13.
URI
http://onlinelibrary.wiley.com/doi/10.1002/art.39228/abstracthttp://hdl.handle.net/20.500.11754/28395
ISSN
2326-5191; 2326-5205
DOI
10.1002/art.39228
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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