The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese

J. A. Todd, Yoshinori Fukui, T. Kltagawa, Takehiko Sasazuki

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Abstract

Analysis of the frequencies of class II HLA-DR and HLA-DQ alleles by serological and DNA typing in 49 Japanese patients with type 1 (insulin-dependent) diabetes and 31 Japanese controls indicates the following, (i) Susceptibility is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion. (ii) Of the class II alleles detected, the A3 allele of the DQA1 locus was the most strongly associated with disease. Ninety-six percent of the patients were positive for the A3 allele compared to 53% of the controls (P = 0.001; relative risk = 19.7; confidence limits = 3.72-188.64). (iii) The DQw8 allele of the DQB1 locus, which is associated with susceptibility to type 1 diabetes in Caucasians and Blacks, was not increased in frequency in Japanese patients (22%) versus controls (19%). (iv) Asp-57-encoding DQB1 alleles are associated with reduced susceptibility to type 1 diabetes in Caucasians. The major predisposing haplotypes in Japanese are DR4 and DR9. By DNA sequence analysis, both of these Japanese haplotypes have Asp-57-encoding DQB1 alleles. Oligonucleotide dot blot analysis showed that all, except 1, of the 49 Japanese patients and all of the 31 controls have at least one Asp-57-encoding DQB1 allele. In addition, 40% of the patients were homozygous for Asp-57-encoding DQB1 alleles versus 35% of the controls. The high frequencies of Asp-57-encoding DQB1 alleles in this ethnic group may account for the rarity of type 1 diabetes in Japan.

Original languageEnglish
Pages (from-to)1094-1098
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number3
DOIs
Publication statusPublished - Jan 1 1990

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Type 1 Diabetes Mellitus
Alleles
HLA-DQ Antigens
HLA-DR Antigens
Haplotypes
HLA-DQA1 antigen
DNA Fingerprinting
DNA Sequence Analysis
Ethnic Groups
Oligonucleotides
Japan
Insulin

All Science Journal Classification (ASJC) codes

  • General

Cite this

The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese. / Todd, J. A.; Fukui, Yoshinori; Kltagawa, T.; Sasazuki, Takehiko.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 3, 01.01.1990, p. 1094-1098.

Research output: Contribution to journalArticle

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abstract = "Analysis of the frequencies of class II HLA-DR and HLA-DQ alleles by serological and DNA typing in 49 Japanese patients with type 1 (insulin-dependent) diabetes and 31 Japanese controls indicates the following, (i) Susceptibility is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion. (ii) Of the class II alleles detected, the A3 allele of the DQA1 locus was the most strongly associated with disease. Ninety-six percent of the patients were positive for the A3 allele compared to 53{\%} of the controls (P = 0.001; relative risk = 19.7; confidence limits = 3.72-188.64). (iii) The DQw8 allele of the DQB1 locus, which is associated with susceptibility to type 1 diabetes in Caucasians and Blacks, was not increased in frequency in Japanese patients (22{\%}) versus controls (19{\%}). (iv) Asp-57-encoding DQB1 alleles are associated with reduced susceptibility to type 1 diabetes in Caucasians. The major predisposing haplotypes in Japanese are DR4 and DR9. By DNA sequence analysis, both of these Japanese haplotypes have Asp-57-encoding DQB1 alleles. Oligonucleotide dot blot analysis showed that all, except 1, of the 49 Japanese patients and all of the 31 controls have at least one Asp-57-encoding DQB1 allele. In addition, 40{\%} of the patients were homozygous for Asp-57-encoding DQB1 alleles versus 35{\%} of the controls. The high frequencies of Asp-57-encoding DQB1 alleles in this ethnic group may account for the rarity of type 1 diabetes in Japan.",
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