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

Arthritis Rheum. 2009 Dec;60(12):3807-14. doi: 10.1002/art.24982.


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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / blood
  • Child
  • Child, Preschool
  • DNA / genetics
  • DNA / 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
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Young Adult


  • Autoantibodies
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • DNA
  • DNA Polymerase II
  • DNA Topoisomerases, Type I