Transcomplementation of HLA DQA1-DQB1 in DR3/DR4 and DR3/DR9 Heterozygotes and IDDM in Taiwanese Families

Lee Ming Chuang; Huey Peir Wu; Wen Yu Tsai; Boniface J Lin; Tong Yuan Tai

doi:10.2337/diacare.18.11.1483

Short Reports

Transcomplementation of HLA DQA1-DQB1 in DR3/DR4 and DR3/DR9 Heterozygotes and IDDM in Taiwanese Families

Lee Ming Chuang, MD, PHD,
Huey Peir Wu, MD,
Wen Yu Tsai, MD,
Boniface J Lin, MD and
Tong Yuan Tai, MD, PHD

Departments of Internal Medicine, College of Medicine, National Taiwan University Taipei, Taiwan
Departments of Pediatrics, College of Medicine, National Taiwan University Taipei, Taiwan
Graduate Institutes of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan

Address correspondence and reprint requests to Tong-Yuan Tai, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S. Rd., Taipei, Taiwan.

Diabetes Care 1995 Nov; 18(11): 1483-1486. https://doi.org/10.2337/diacare.18.11.1483

Abstract

OBJECTIVE To study the human leukocyte antigen (HLA)-DQ heterodimers in the susceptible DR haplotypes for patients with insulin-dependent diabetes mellitus (IDDM) in Taiwan.

RESEARCH DESIGN AND METHODS Extended class II HLA haplotypes were studied in 57 unrelated IDDM patients, 31 simplex IDDM families, and 105 unrelated control subjects recruited from the same area in Taiwan. Class II HLA genotyping was based on PCR-SSO DNA typing techniques. Extended class II HLA haplotypes were deduced unequivocally by the Taiwanese pedigree studies.

RESULTS DR3/DR3, DR3/DR4, and DR3/DR9 genotypes were strongly associated with IDDM susceptibility in this population. In addition to the reported DR3/DR4 in Caucasians, the heterozygotic effect of DR3/DR9 for IDDM was remarkable in the Taiwanese population. Extended HLA haplotypes studies revealed that DRB1*0301/DQA1*0501/DQB1*0201, DRB1*0405/DQA1*0301/DQB1*0302, and DRB1*0405/DQA1*0301/DQB1*0401 were the susceptible haplotypes in this population. There were several hypothetical ways to produce susceptible HLA-DQ heterodimers to explain the susceptibility carried by DR3/DR4 and DR3/DR9 genotypes. Among all DR4 subtypes, only DRB1*0405 was associated with the increased risk of IDDM.

CONCLUSIONS These data strongly suggest that the HLA-DR-associated IDDM susceptibility is most likely explained by the formation of the susceptible DQ heterodimers encoded by the DQA1/DQB1 either in cis or in trans.