Transcomplementation of HLA DQA1-DQB1 in DR3/DR4 and DR3/DR9 heterozygotes and IDDM in Taiwanese families.
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.


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.
Chuang
L M
LM
Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Wu
H P
HP
Tsai
W Y
WY
Lin
B J
BJ
Tai
T Y
TY
D016001:Confidence Intervals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D005006:Ethnicity; D005190:Family; D005816:Genetic Complementation Test; D005838:Genotype; D006683:HLA-DQ Antigens / Q000097:blood / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen / Q000097:blood / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000097:blood / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D016133:Polymerase Chain Reaction; D044469:Racial Groups; D012016:Reference Values; D013624:Taiwan
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; C038988:HLA-DR9 antigen