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HLA-DPB1 and DPB2 Are Genetic Loci for Systemic Sclerosis - A Genome-Wide Association Study in Koreans With Replication in North Americans

Cited 82 time in Web of Science Cited 83 time in Scopus
Authors
Zhou, Xiaodong; Lee, Jong Eun; Arnett, Frank C.; Xiong, Momiao; Yoo, Yeon Kyeong; Reveille, John D.; Kim, Jin Hyun; Choi, Ji Yong; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook; Lee, Eun Young; Park, Ji Ah; Song, Ran; Mayes, Maureen D.; Shin, Eun Soon; Park, Min Young
Issue Date
2009-12
Publisher
WILEY-LISS
Citation
ARTHRITIS AND RHEUMATISM; Vol.60 12; 3807-3814
Abstract
Objective. To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. Methods. A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population. Results. The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1. and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P = 8.16 X 10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P = 7.61 x 10(-8)) and DPB1*0901. (P = 2.55 x 10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P = 7.58 x 10(-17)/4.84 x 10(-16)) or anticentromere autoantibodies (P = 1.12 x 10(-3)/3.2 x 10(-5)), respectively. Conclusion. The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies.
ISSN
0004-3591
Language
English
URI
http://hdl.handle.net/10371/77393
DOI
https://doi.org/10.1002/art.24982
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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