IKBL promoter polymorphism is strongly associated with resistance to type 1 diabetes in Japanese.
Type 1 diabetes is a multifactorial disease in which the genes of the major histocompatibility complex (MHC) play a key role. Recently, non-human leukocyte antigen (non-HLA) genes in the class III region of this complex have been presumed to be associated with type 1 diabetes by linkage analyses. We investigated the possibility of the inhibitor of kappaB-like (IKBL, also known as 'NFKBIL1') gene as one of these candidates. We carried out a case-control study of 124 patients with type 1 diabetes and 330 healthy control subjects. The haplotypes of the IKBL promoter, i.e., PA (-263A, -63T), PB (-263A, -63A), PC (-263G, -63T), were assigned by the single-nucleotide polymorphisms at positions -263 and -63 from the transcription start site. The frequency of the wild-type haplotype, PA, was elevated, while that of the variant-type haplotype, PC, was lower in patients than controls. In two-locus analyses with HLA-DRB1 alleles, the PA haplotype showed linkage disequilibrium with the DRB1*0405 allele and the PC haplotype with the DRB1*1502 allele. A notable observation was that the PC haplotype was significantly associated with protection in the DRB1*1502-negative population. Our study indicates the first evidence of a possible independent association between type 1 diabetes and polymorphisms in the promoter of the IKBL gene.
Department of Anatomy, Biology and Medicine (Internal Medicine I), Oita Medical University School of Medicine, Oita, Japan. khamaguc@med.oita-u.ac.jp
T
T
Yamashita
K
K
Hamaguchi
Y
Y
Kusuda
A
A
Kimura
T
T
Sakata
H
H
Yoshimatsu
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D007223:Infant; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; C120111:NFKBIL1 protein, human