Genetics in the prediction of insulin-dependent diabetes mellitus: from theory to practice.

Only weak associations have been found for particular environmental factors and development of insulin-dependent diabetes mellitus (IDDM). Very few studies have, however, accounted for genetic susceptibility when cases and controls have been compared. The genetics of IDDM is complex, but the HLA-DQ genes are the most important. There are many different combinations of DQA1 and DQB1 genes conferring disease risk to differing degrees. The strategy of NOBADIA (Norwegian Babies against Diabetes) is to identify at birth the babies in the general population with the highest genetic risk for developing IDDM: those carrying DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 (for simplification, hereafter named DQ2/DQ8). Four per cent of Norwegian babies carry this genotype which accounts for 46% of future cases of IDDM. Babies carrying the IDDM high-risk genotype have a lifetime risk of 12% for developing the disease. This is very close to the risk of a first-degree relative with the same genotype. DQ2/DQ8 heterozygotes also acquire the disease earlier than those with a lower genetic risk. Parents of children carrying the DQ2/DQ8 genotype will be informed and offered regular follow-up with blood samples and questionnaires at their public health care centre.