Differential HLA Contribution from Fathers Versus Mothers to IDDM Susceptibility
It is well established that people with insulin-dependent diabetes mellitus (IDDM) who are of European ancestry have elevated frequencies of phenotypes positive for HLA-DR3 and DR4. In other words, HLA-DR3 and DR4 are associated with increased susceptibility to developing IDDM, either because these genes themselves predispose to disease or genes linked to and in disequilibrium with DR3 and DR4 predispose to disease. For example, in our dataset of 231 diabetics ascertained through the Alberta Children’s Hospital Diabetes Clinic in Calgary, frequencies of patients positive for HLA-DR3 and HLA-DR4 were 63% and 70%, respectively,1 compared with frequencies in the general population of approximately 20% and 29%.2 Only 7% of our diabetics were negative for both DR3 and DR4, compared with approximately 54% of individuals in the general population. Prior to the discovery of insulin, insulin-dependent diabetes was a lethal disorder usually resulting in death prior to the reproductive years. Thus, genes producing susceptibility to IDDM were selected against. It is probable that other compensating advantages of these genes helped to maintain them at relatively high population frequencies.
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- 1.L.L. Field, Non-HLA region genes in insulin-dependent diabetes mellitus (IDDM), in: “The Genetics of Diabetes”, B.D. Tait, L.C. Harrison, eds., W.B. Saunders Co., Baillière’s Clin Endocrinol Metab. 5:413 (1991).Google Scholar