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Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.

Abstract：

:The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin-dependent diabetes mellitus (IDDM), whereas an aspartic acid at this position (Asp-57) appears to confer resistance to the disease. We hypothesize that the 30-fold difference in IDDM incidence across racial groups and countries is related to variability in the frequency of these alleles. Diabetic and nondiabetic individuals were evaluated in five populations, including those at low, moderate, and high risk. HLA-DQ beta genotype distributions among the IDDM case groups were markedly different (P less than 0.001), as were those among nondiabetic controls (P less than 0.001). Non-Asp-57 alleles were significantly associated with IDDM in all areas; population-specific odds ratios for non-Asp-57 homozygotes relative to Asp-57 homozygotes ranged from 14 to 111. Relative risk information from the case-control study and population incidence data were combined to estimate genotype-specific incidence rates for the Allegheny County, PA, Caucasians. These rates were used to predict the overall incidence rates in the remaining populations, which were within the 95% confidence intervals of the actual rates established from incidence registries. These results are consistent with the hypothesis that population variation in the distribution of non-Asp-57 alleles may explain much of the geographic variation in IDDM incidence.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Dorman JS,LaPorte RE,Stone RA,Trucco M

doi

10.1073/pnas.87.19.7370

subject

Has Abstract

pub_date

1990-10-01 00:00:00

pages

7370-4

issue

19

eissn

0027-8424

issn

1091-6490

journal_volume

87

pub_type

杂志文章

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