Low frequency of HLA DRB1*03-DQB1*02 and DQB1*0302 haplotypes in Romania is consistent with the country's low incidence of Type I diabetes

Aims/hypothesis. Our study aimed to determine the association of HLA class II HLA-DQB1 alleles with Type I (insulin-dependent) diabetes mellitus and t he frequencies of these alleles in the Romanian population, which has one o f the lowest incidences of Type I diabetes in children aged 0-14 years in E urope at 3-4 cases per 100 000 person-years. Methods. We used the sequence specific primer-polymerase chain reaction (PC R-SSP) technique to type HLA-DQB1 alleles, the HLA-DRB1 alleles DRB1*03 and one single nucleotide polymorphism (SNP) in the insulin gene (INS). We stu died 204 Type I diabetic Romanian families, 196 of which were simplex with 70.3% of subjects diagnosed under 14 years of age. Data was analysed using a modified version of the Transmission Disequilibrium Test, the Transmissio n Disequilibrium Test itself, and the affected family-based control method. Results. We found, as expected, the strong positive DQB1*02-DRB1*03 and DQB 1*0302, and negative DQB1*0602, HLA class II allele associations with Type I diabetes in these Romanian families. However, using the affected family-b ased control method, we found relatively low population frequencies of DQB1 *02-DRB1*03 and DQB1*0302 alleles in Romania (15.8%) compared with Sardinia (31.3%), a high incidence European region (35 cases per 100 000 person-yea rs in children aged 0-14 years). The INS locus had a strong effect in this data set with 80.5% transmission of the susceptible INS allele from parents to affected siblings (relative risk = 4.1). Conclusion/interpretation. Part of the explanation for the low incidence of Type I diabetes in Romania could be the lower frequency of the DRB1*03-DQB 1*02 and DQB1*0302 susceptibility haplotypes in this country.