Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen-DR9-linked susceptibility to insulin-dependent diabetes mellitus.
DNA sequence analysis of class II HLA from Caucasian and black patients with type 1 (insulin-dependent) diabetes mellitus has suggested that aspartic acid at position 57 (Asp 57) of the DQ beta chain provides protection against insulin-dependent diabetes mellitus (IDDM). In contrast, most Japanese patients with IDDM have Asp 57-positive alleles. To determine the reason for the differences and to localize the HLA-linked diabetogenic gene in Japanese, we studied the DQA1 and DQB1 genes of Japanese patients with IDDM and control subjects by the polymerase chain reaction in combination with restriction fragment length polymorphism analysis. Associations of DQA1*0301 and DQB1*0303 with IDDM were observed. DQA1*01 was associated negatively with IDDM. The HLA-DR9 haplotype, which is associated positively with IDDM in Japanese, was associated with DQA1*0301 and DQB1*0303, indicating that the Japanese DR9 haplotype is the same as that in caucasians but different from that in blacks. Of the loci on Japanese DR9 haplotypes, the DQA1*0301 allele showed the highest association with IDDM. DQB1*0303 was also positively associated with IDDM. Since DQB1*0303 is identical to DQB1*0302 except that it contains Asp 57, the data suggests that an Asp 57-positive allele confers susceptibility to IDDM when the whole molecule of the DQ beta chain is similar to other susceptible DQ beta chains. DQA1*0301 appears to be a marker of IDDM in all these populations: Japanese, caucasian, and black.
Department of Geriatric Medicine, Osaka University Medical School, Japan.
H
H
Ikegami
Y
Y
Kawaguchi
E
E
Yamato
S
S
Kuwata
K
K
Tokunaga
Y
Y
Noma
K
K
Shima
T
T
Ogihara
D000328:Adult; D000375:Aging; D000483:Alleles; D044466:Asian People; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005796:Genes; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000032:analysis; D006683:HLA-DQ Antigens / Q000032:analysis / Q000737:chemistry; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D006680:HLA Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C038988:HLA-DR9 antigen; D015335:Molecular Probes