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
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.
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:.
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.