title: Rare human leukocyte antigen genotype in two siblings with type 1 diabetes in a Japanese family clustered with type 1 diabetes.
abstract: Multiplex families with type 1 diabetes are important for identification of rare variants that cannot be identified in case-control association studies. The very low incidence of type 1 diabetes in the Japanese population, however, makes identification of such families difficult. We identified a Japanese family in which three members developed type 1 diabetes, and studied the genotype of the human leukocyte antigen. All three members with type 1 diabetes had the DRB1*08:02-DQB1*03:02 haplotype, which is specific to the Asian population and strongly susceptible for type 1 diabetes. In particular, a proband and his sister had the same genotype, DRB1*08:02-DQB1*03:02/DRB1*08:02-DQB1*03:02, which is extremely rare even in the Japanese population. Both parents also had DRB1*08:02-DQB1*03:02, but in combination with different human leukocyte antigen haplotypes. Weakly susceptible DRB1*13:02-DQB1*06:04 was present in the affected mother, and resistant DRB1*15:01-DQB1*06:02 in the unaffected father. These data suggest DRB1*08:02-DQB1*03:02 to be a contributing factor for familial clustering of type 1 diabetes in this family.
authors.affiliation: Department of Diabetes and Endocrinology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Ina
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.affiliation: Department of Diabetes and Endocrinology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakamoto
authors.affiliation: Department of Diabetes and Endocrinology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Sekiguchi
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
mesh_terms: D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D006680:HLA Antigens
keywords: Genetic susceptibility; Human leukocyte antigen haplotype; Type 1 diabetes