HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans.
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=8.16x10(-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.


CONCLUSIONS
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.
Zhou
Xiaodong
X
University of Texas Health Science Center at Houston, Houston, TX, USA.
Lee
Jong Eun
JE
Arnett
Frank C
FC
Xiong
Momiao
M
Park
Min Young
MY
Yoo
Yeon Kyeong
YK
Shin
Eun Soon
ES
Reveille
John D
JD
Mayes
Maureen D
MD
Kim
Jin Hyun
JH
Song
Ran
R
Choi
Ji Yong
JY
Park
Ji Ah
JA
Lee
Yun Jong
YJ
Lee
Eun Young
EY
Song
Yeong Wook
YW
Lee
Eun Bong
EB
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004257:DNA Polymerase II / Q000235:genetics*; D004264:DNA Topoisomerases, Type I / Q000276:immunology; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D004247:DNA; D004257:DNA Polymerase II; D004264:DNA Topoisomerases, Type I