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HLA‐class II and class I genotypes among Japanese children with Type 1A diabetes and their families
Author(s) -
Sugihara Shigetaka,
Ogata Tsutomu,
Kawamura Tomoyuki,
Urakami Tatsuhiko,
Takemoto Koji,
Kikuchi Nobuyuki,
Takubo Noriyuki,
Tsubouchi Kohji,
Horikawa Reiko,
Kobayashi Kisho,
Kasahara Yoshihito,
Kikuchi Tohru,
Koike Akemi,
Mochizuki Takahiro,
Minamitani Kanshi,
Takaya Ryuzo,
Mochizuki Hiroshi,
Nishii Aki,
Yokota Ichiro,
Kizaki Zenro,
Mori Tetsuo,
Shimura Naoto,
Mukai Tokuo,
Matsuura Nobuo,
Fujisawa Takao,
Ihara Kenji,
Kosaka Kitaro,
Kizu Rika,
Takahashi Toshikazu,
Matsuo Satoshi,
Hanaki Keiichi,
Igarashi Yutaka,
Sasaki Goro,
Soneda Shun,
Teno Shinichi,
Kanzaki Susumu,
Saji Hiroh,
Tokunaga Katsushi,
Amemiya Shin
Publication year - 2012
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/j.1399-5448.2011.00833.x
Subject(s) - medicine , human leukocyte antigen , type 1 diabetes , class (philosophy) , genotype , genetics , diabetes mellitus , immunology , gene , biology , endocrinology , antigen , artificial intelligence , computer science
Sugihara S, Ogata T, Kawamura T, Urakami T, Takemoto K, Kikuchi N, Takubo N, Tsubouchi K, Horikawa R, Kobayashi K, Kasahara Y, Kikuchi T, Koike A, Mochizuki T, Minamitani K, Takaya R, Mochizuki H, Nishii A, Yokota I, Kizaki Z, Mori T, Shimura N, Mukai T, Matsuura N, Fujisawa T, Ihara K, Kosaka K, Kizu R, Takahashi T, Matsuo S, Hanaki K, Igarashi Y, Sasaki G, Soneda S, Teno S, Kanzaki S, Saji H, Tokunaga K, Amemiya S, and The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT). HLA‐class II and class I genotypes among Japanese children with Type 1A diabetes and their families. Objective: To determine the HLA‐DRB1, DQB1, DPB1, A, C, and B genotypes among Japanese children with autoimmune type 1 diabetes. Methods: Four hundred and thirty patients who were GADAb and/or IA‐2Ab‐positive (Type 1A) were recruited from 37 medical centers as part of a nationwide multicenter collaborative study. DNA samples from 83 siblings of the children with Type 1A diabetes and 149 parent–child trios were also analyzed. A case‐control study and a transmission disequilibrium test (TDT) were then performed. Results: The susceptible and protective DRB1 and DQB1 alleles and haplotypes were confirmed. DPB1 alleles unique to the Japanese population and those common to multiple ethnic groups were also present. A linkage disequilibrium (LD) analysis showed both susceptible and protective haplotypes. The TDT did not reveal any alleles that were transmitted preferentially from the mother or father to children with Type 1A. Homozygosity for DRB1∗09:01‐DQB1∗03:03 and heterozygosity for DRB1∗04:05‐DQB1∗04:01 and DRB1∗08:02‐DQB1∗03:02 were associated with an extremely high risk of Type 1A. A comparison of children with Type 1A and their parents and siblings suggested a dose effect of susceptible DRB1‐DQB1 haplotypes and an effect of protective alleles on immunological pathogenesis. DRB1∗09:01 appeared to be strongly associated with an early onset in preschool children with Type 1A diabetes. Conclusions: This study demonstrated the characteristic association of HLA‐class II and class I genes with Type 1A diabetes among Japanese children. A TDT did not reveal the genomic imprinting of HLA‐class II and class I genes in Type 1A diabetes.