Parental Origin of Diabetes-Associated HLA Types in Sibling Pairs With Type I Diabetes

Genetic susceptibility to type I diabetes is partly determined by genes located in the human leukocyte antigen (HLA) region on chromosome 6. It has been claimed that the transmission of HLA-encoded susceptibility is influenced by parental sex. Fathers are reported to transmit HLA-DR4 haplotypes more frequently to their diabetic offspring than mothers. More recently, it has been suggested that the presence of HLA-DR4 in a mother may influence susceptibility in her offspring, even when it is not inherited. We have analyzed 172 multiplex diabetic pedigrees from the U.K. and find no evidence to support an important effect of parental sex on the inheritance of HLA-encoded susceptibility. Examination of a further 110 pedigrees from the U.S. supports this finding. These results have important implications for strategies involving genetic screening for type I diabetes.