HLA Studies in Diabetes Mellitus: A Review

This chapter presents a review of HLA studies in diabetes mellitus, and finds that the presence of one or both of the B and D loci is necessary but not sufficient for IDDM to develop, as environmental stimuli are required as triggering mechanisms.

Abstract

Publisher Summary The chapter presents a review of HLA studies in diabetes mellitus. Insulin-dependent diabetes mellitus (IDDM) is a disease entity in itself. It is different from noninsulin-dependent diabetes and other types of diabetes mellitus in etiology and pathogenesis. HLA-B8 is associated with IDDM in all Caucasion populations, irrespective of the age of onset of the disease. HLA-Bwl5 is associated with IDDM in populations of Northern European and British origin, while B18 seems to replace Bwl5 in Southern European populations. IDDM is uncommon in populations where the HLA-B8 frequency is low, and in the Japanese IDDM occurs in association with Bw22. The HLA-Dw3 and Dw4 association with IDDM is stronger than that of the B alleles. In families, the phenotype IDDM segregates with a certain genotype, namely, the diabetic proband's HLA haplotype. Only a small proportion of family members carrying the diabetic haplotype develop IDDM. Within the HLA region, between the B and D loci are located two diabetogenic genes. The presence of one or both of these genes is necessary but not sufficient for IDDM to develop, as environmental stimuli are required as triggering mechanisms.