title: HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans.
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=8.16x10(-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.
authors: University of Texas Health Science Center at Houston, Houston, TX, USA.
authors: Xiaodong
authors: X
authors: Zhou
authors: Jong Eun
authors: JE
authors: Lee
authors: Frank C
authors: FC
authors: Arnett
authors: Momiao
authors: M
authors: Xiong
authors: Min Young
authors: MY
authors: Park
authors: Yeon Kyeong
authors: YK
authors: Yoo
authors: Eun Soon
authors: ES
authors: Shin
authors: John D
authors: JD
authors: Reveille
authors: Maureen D
authors: MD
authors: Mayes
authors: Jin Hyun
authors: JH
authors: Kim
authors: Ran
authors: R
authors: Song
authors: Ji Yong
authors: JY
authors: Choi
authors: Ji Ah
authors: JA
authors: Park
authors: Yun Jong
authors: YJ
authors: Lee
authors: Eun Young
authors: EY
authors: Lee
authors: Yeong Wook
authors: YW
authors: Song
authors: Eun Bong
authors: EB
authors: Lee
mesh_terms: 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
chemical_list: 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