Type 1 diabetes genetic susceptibility encoded by HLA DQB1 genes in Romania

Abstract

Most cases of type 1 diabetes (T1DM) are due to an immune-mediated destruction of the pancreatic beta cells, a process that is conditioned by multiple genes and environmental factors. The main susceptibility genes are represented by the class II HLA-DRB1 and DQB1 alleles. The aim of our study was to reconfirm the contribution of HLA-DQB1 polymorphisms to T1DM genetic susceptibility for the Romanian population. For this, 219 Romanian T1DM families were genotyped at high resolution for HLA DQB1 using the PCR-SSOP method (Polymerase Chain Reaction - Sequence Specific Oligonucleotide Probes). Allele transmission to diabetics and unaffected siblings was studied using the Transmission Disequilibrium Test (TDT). We found an increased transmission of DQB1*02 (77.94% transmission, pTDT = 7.18 × 10 -11) and DQB1*0302 (80.95% transmission, pTDT = 2.25 × 10-10) alleles to diabetics, indicating the diabetogenic effect of these alleles. Conversely, DQB1*0301, DQB1*0603, DQB1*0602, DQB1*0601 and DQB1*05 alleles are protective, being significantly less transmitted to diabetics. In conclusion, our results confirmed the strong effect of HLA-DQB1 alleles on diabetes risk In Romania, with some characteristics which can contribute to the low incidence of T1DM in this country.