Originals

Diabetologia

, Volume 36, Issue 3, pp 234-238

First online:

HLA-associated susceptibility to Type 2 (non-insulin-dependent) diabetes mellitus: the Wadena City Health Study

  • S. S. RichAffiliated withDepartment of Laboratory Medicine and Pathology and Institute of Human Genetics, University of Minnesota
  • , L. R. FrenchAffiliated withChronic Disease and Environmental Epidemiology Section, Minnesota Department of Health, University of Minnesota
  • , J. M. SprafkaAffiliated withDivision of Epidemiology, University of Minnesota
  • , J. P. ClementsAffiliated withChronic Disease and Environmental Epidemiology Section, Minnesota Department of Health, University of Minnesota
  • , F. C. GoetzAffiliated withDepartment of Medicine, University of Minnesota

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Summary

Epidemiologic data suggest that a parental history of Type 2 (non-insulin-dependent) diabetes mellitus increases the risk of Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 and Type 2 diabetes. We have previously reported evidence that HLA-DR4-linked factors may represent a homogeneous subset of diabetes susceptibility. First, HLA-DR4 frequency was higher in Type 1 diabetic study subjects with a Type 2 diabetic parent than in Type 1 diabetic subjects whose parents were not diabetic. Second, a DR4-haplotype was transmitted from the Type 2 diabetic parent to the Type 1 offspring more often than expected. These data are consistent with the hypothesis that families with a Type 2 diabetic parent and Type 1 diabetic child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility. In this report, we further explore the relationship between the high-risk HLA antigen (HLA-DR4) in study subjects with differing glycaemic status (National Diabetes Data Group criteria). In this community-based study, we find evidence that HLA-DR4 is increased in study subjects with Type 2 diabetes and may be a marker for Type 2 diabetes susceptibility.

Key words

Genetics Type 2 (non-insulin-dependent) diabetes mellitus HLA