Asian-Specific HLA Haplotypes Reveal Heterogeneity of the Contribution of HLA-DR and -DQ Haplotypes to Susceptibility to Type 1 Diabetes.
- Yumiko Kawabata1,
- Hiroshi Ikegami1,
- Yoshihiko Kawaguchi1,
- Tomomi Fujisawa1,
- Maki Shintani1,
- Masaya Ono1,
- Masanori Nishino1,
- Yasuko Uchigata2,
- Inkyu Lee3 and
- Toshio Ogihara1
- 1Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- 2Diabetes Center, Tokyo Women’s Medical College, Tokyo, Japan
- 3Department of Medicine, Medical Research Institute, Keimyung University Medical School, Keimyung, Korea
Abstract
To assess the effect of Asian-specific HLA haplotypes on susceptibility to type 1 diabetes, we investigated the association of genotypic combinations of DRB1-DQB1 haplotypes with susceptibility to type 1 diabetes. We studied 132 Japanese patients with type 1 diabetes and 157 control subjects, along with 67 Korean patients and 109 control subjects. DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 were confirmed to be two major susceptible HLA haplotypes in the Japanese population. The frequencies of heterozygotes and homozygotes with DRB1*0405-DQB1*0401 were similarly higher in patients than in control subjects (homozygotes, 5.3% vs. 3.8%; heterozygotes, 48.5% vs. 26.1%). In contrast, homozygotes, but not heterozygotes, with DRB1*0901-DQB1*0303 were more frequent in patients with type 1 diabetes than in control subjects (homozygotes, 12.9% vs. 0.6%; heterozygotes, 22.0% vs. 24.8%). A similar tendency was also observed in the Korean population. In multiple logistic regression analysis, DRB1*0405-DQB1*0401 fitted a dominant model and DRB1*0901-DQB1*0303 fitted a recessive model. These data, which indicate that the contribution of HLA haplotypes to the genetic susceptibility to type 1 diabetes differs depending on the genotypic combination of HLA haplotypes, suggest the importance of extensive analysis of genotypes in studies on HLA and disease association in general.
Footnotes
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Address correspondence and reprint requests to H. Ikegami, Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: ikegami{at}geriat.med.osaka-u.ac.jp.
Received for publication 29 March 2001 and accepted in revised form 5 November 2001.
AIC, Akaike’s information criterion; MHC, major histocompatibility complex; OR, odds ratio; Pc, corrected P value.
