title: Asian-specific HLA haplotypes reveal heterogeneity of the contribution of HLA-DR and -DQ haplotypes to susceptibility to type 1 diabetes.
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.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Maki
authors.initials: M
authors.lastname: Shintani
authors.forename: Masaya
authors.initials: M
authors.lastname: Ono
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishino
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Uchigata
authors.forename: Inkyu
authors.initials: I
authors.lastname: Lee
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D007723:Korea; D008297:Male; D008875:Middle Aged; D010641:Phenotype
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens