A second component of HLA-linked susceptibility to type 1 diabetes maps to class I region.
Type 1 diabetes is a polygenic disease with a major susceptibility locus, IDDM1, located in the human leukocyte antigen (HLA) region. Although class II loci, DR and DQ genes in particular, are major components of IDDM1, accumulating lines of evidence indicated that IDDM1 consists of multiple components and that non-class II genes in addition to class II genes contribute to susceptibility to and/or age-at-onset of type 1 diabetes. To identify a second component of IDDM1, we investigated the association of a panel of polymorphisms in 2.2 Mb region of the HLA encompassing from class II to class I regions with type 1 diabetes. Polymorphisms types were: DRB1 and DQB1 in class II; two microsatellite markers, BAT2-GT and TNFa in class III; and, five microsatellite markers, STR-MICA, MIB, C1-3-1, C2-4-4, and C3-2-10 in class I region. A total of >200 Japanese patients and healthy control subjects were studied. Class II DRB1*0405 and DQB1*0401 were significantly associated with susceptibility to, but not with age-at-onset of, type 1 diabetes. C1-3-1, located near C locus, was significantly associated with not only susceptibility to, but also age-at-onset of type 1 diabetes. These data suggest that a second component of IDDM1 maps to the HLA class I region, contributing to susceptibility to as well as age-at-onset of type 1 diabetes.
Kawabata
Yumiko
Y
Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Ikegami
Hiroshi
H
Fujisawa
Tomomi
T
Noso
Shinsuke
S
Asano
Katsuaki
K
Hiromine
Yoshihisa
Y
Ogihara
Toshio
T
D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007564:Japan; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D005819:Genetic Markers; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I