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PMID: 19950302 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans.

Arthritis and rheumatism ·Vol. 60 ·No. 12 ·2009-12-00 ·Pages 3807-14

Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, Shin ES, Reveille JD, Mayes MD, Kim JH, Song R, Choi JY, Park JA, Lee YJ, Lee EY, Song YW, Lee EB

Abstract

To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. 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. 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=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-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=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively. 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.

MeSH Terms
Adolescent Adult Aged Autoantibodies/blood Child Child, Preschool DNA/genetics,isolation & purification DNA Polymerase II/genetics DNA Topoisomerases, Type I/immunology Female Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study HLA-DP Antigens/genetics HLA-DP beta-Chains Humans Korea/epidemiology Male Middle Aged North America/epidemiology Polymorphism, Single Nucleotide Scleroderma, Systemic/ethnology,genetics,immunology Young Adult
Chemicals
Autoantibodies HLA-DP Antigens HLA-DP beta-Chains HLA-DPB1 antigen DNA DNA Polymerase II DNA Topoisomerases, Type I
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Zhou Xiaodong
University of Texas Health Science Center at Houston, Houston, TX, USA.
Lee Jong Eun
Arnett Frank C
Xiong Momiao
Park Min Young
Yoo Yeon Kyeong
Shin Eun Soon
Reveille John D
Mayes Maureen D
Kim Jin Hyun
Song Ran
Choi Ji Yong
Park Ji Ah
Lee Yun Jong
Lee Eun Young
Song Yeong Wook
Lee Eun Bong
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Article Info
Journal
Arthritis and rheumatism
Abbr.
Arthritis Rheum
ISSN
0004-3591
DOI
10.1002/art.24982
Published
2009-12-00
Pages
3807-14
Language
English
Region
United States
NLM ID
0370605
PMCID
PMC2829245
Subset
IM
Grants
NIAMS NIH HHS · P50 AR054144 · United States
NIAMS NIH HHS · P50-AR-054144 · United States
NIAMS NIH HHS · P50 AR054144-03S1 · United States
NCRR NIH HHS · UL1 RR024148 · United States
NCRR NIH HHS · UL1-RR-024148 · United States
NIAMS NIH HHS · N01AR02251 · United States
NIAMS NIH HHS · R01 AR055258 · United States
External Links
PubMed source DOI: 10.1002/art.24982 PMC Full Text View journal details
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