HLA-DQA and DQB Alleles and Predisposition to Insulin Dependent Diabetes Mellitus

Type I insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease. Onset of the disease is attributed to interplay between genetic and environmental risk factors. It is strongly associated with the presence of arginine in position 52 of DQ alpha (α) chain and the absence of aspartic acid in position 57 of the DQ beta (β) chain. In this study we assessed the relative contribution of DQ α and DQ β chains to susceptibility to type I diabetes among the Egyptian patients. We identified those genetically at risk of development among their siblings in order to detect early development of autoantibodies allowing early application of preventive programs. Genomic DNA of forty Egyptian type I IDDM patients , 13 non diabetic siblings and 22 non diabetic controls were amplified using polymerase chain reaction- amplification refractory mutation system (ARMS) and genotyped for HLA-DQA and DQB alleles. A significant high frequency of homozygous genotype for DQB1 non- Asp allele was detected in patients 50%, p=0.01, odd ratio (OR) =10 at 95% confidence interval (CI) =2.1-48.6 with susceptible results to the disease. The frequency of diabetogenic heterodimer Arg/non-Asp was significantly high in patients (82%, p=0.044, OR= 3.26, at 95% CI= 1.005-10.6). On the other hand, a significant lower frequency of homozygous genotype for DQB1 Asp allele was detected in patients 12.5%, p=0.065; it was associated with protection from the disease. In conclusion, in Egyptian patients susceptibility and protection from type I diabetes is mainly associated with the DQβ chain. Siblings have potential risk to the disease. Non affected siblings should be targeted in a larger study for counselling. At risk individuals should be subjected to regular monitoring for the early development of autoantibodies which start years before the overt diabetes.