Diabetologia

, Volume 34, Issue 5, pp 350–355

Shared genetic susceptibility of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus: contributions of HLA and haptoglobin

  • S. S. Rich
  • S. S. Panter
  • F. C. Goetz
  • B. Hedlund
  • J. Barbosa
Originals

Summary

Epidemiologic data suggest that having a parent with Type 2 (non-insulin-dependent) diabetes mellitus increases the risk for 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 diabetes and Type 2 diabetes. We contrast genetic risk factors in three sets of families, consisting of (1) a single Type 1 diabetic child (proband) and non-diabetic parents, (2) multiple Type 1 diabetic siblings and non-diabetic parents, and (3) at least one Type 1 diabetic child and at least one Type 2 diabetic parent. Previous studies have demonstrated that HLA region genes, which elevate the risk in Type 1 diabetes, have no significant effect with respect to the risk for developing Type 2 diabetes. An earlier report cited a contribution by the haptoglobin locus to genetic susceptibility for Type 2 diabetes. We provide evidence that a high risk HLA antigen (HLA-DR3) is decreased to a greater extent in Type 1 patients with a Type 2 parent than in Type 1 patients in which the parents are not diabetic. The role of HLA-DR4 is maintained in these families, with an unexpectedly significant increased rate of transmission of the HLA-DR4 allele from Type 2 parent to Type 1 offspring. The role of haptoglobin in these families does not appear to be important, either with respect to association with diabetes or with respect to linkage with a secondary susceptibility locus. These results indicate that families with a Type 2 parent and Type 1 child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility.

Key words

Genetics Type 1 (insulin-dependent) diabetes mellitus Type 2 (non-insulin-dependent) diabetes mellitus HLA haptoglobin 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • S. S. Rich
    • 1
    • 2
  • S. S. Panter
    • 1
  • F. C. Goetz
    • 3
  • B. Hedlund
    • 4
  • J. Barbosa
    • 3
  1. 1.Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA
  2. 2.Institute of Human GeneticsUniversity of MinnesotaMinneapolisUSA
  3. 3.Division of Endocrinology and Metabolism, Department of MedicineUniversity of MinnesotaMinneapolisUSA
  4. 4.Biomedical Frontiers, Inc.MinneapolisUSA

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