Genetic analysis of HLA class II alleles and susceptibility to type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.
Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1 (insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR7.8, pc less than 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0, pc less than 0.001); and (3) although the DRw8-DQw8 haplotype was positively associated with Type 1 diabetes, the DRB1*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese.
Awata
T
T
Division of Endocrinology and Metabolism, Jichi Medical School, Tochigi, Japan.
Kuzuya
T
T
Matsuda
A
A
Iwamoto
Y
Y
Kanazawa
Y
Y
D000483:Alleles; D000595:Amino Acid Sequence; D001224:Aspartic Acid; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes
D006681:HLA-D Antigens; D015345:Oligonucleotide Probes; D001224:Aspartic Acid