HLA-DQA1*0501 is associated with diffuse systemic sclerosis in Caucasian men

Arthritis Rheum. 2000 Sep;43(9):2005-10. doi: 10.1002/1529-0131(200009)43:9<2005::AID-ANR11>3.0.CO;2-#.


Objective: Systemic sclerosis (SSc) is uncommon in men, and relatively little is known about factors contributing to its pathogenesis in this population. In the current study, we investigated HLA class II alleles in men with SSc. We also investigated the hypothesis that HLA compatibility of the mother could be a risk factor for SSc in men.

Methods: Sequence-specific oligonucleotide probe typing was used to determine DQA1, DQB1, and DRB1 alleles of SSc patients (50 men and 36 parous women), healthy controls (59 men and 80 parous women), 26 mothers of men with SSc, and 44 mothers of healthy men. All study subjects were Caucasian, and allele frequencies were compared with those of Caucasian controls from the Eleventh International Histocompatibility Workshop as well as those of local controls.

Results: The DQA1*0501 allele was significantly increased among men with SSc compared with healthy men (odds ratio [OR] 2.3, P = 0.006, Pcorr = 0.04). DQA1*0501 was associated with diffuse SSc in men (OR 3.0, P = 0.004, Pcorr = 0.03), but not with limited SSc in men. Maternal HLA compatibility was not a risk factor for SSc in men.

Conclusion: Previous studies have shown associations of DRB1 alleles with SSc, but have rarely determined DQA1 allele frequencies. Our findings indicate that a specific DQA1 allele is associated with SSc, and that DRB1 associations may be due to linkage disequilibrium with DQA1. Moreover, by analyzing genetic susceptibility according to sex, we found that the contribution of HLA genes to the risk of SSc was substantially greater in men than in parous women.

Publication types

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

MeSH terms

  • Alleles
  • Female
  • HLA-DQ Antigens / genetics*
  • HLA-DQ alpha-Chains
  • Histocompatibility / physiology
  • Humans
  • Male
  • Mothers
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology*
  • Sex Factors
  • White People / genetics*


  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen