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AIMS/HYPOTHESIS: Our study aimed to determine the association of HLA class II HLA-DQB1 alleles with Type I (insulin-dependent) diabetes mellitus and the frequencies of these alleles in the Romanian population, which has one of the lowest incidences of Type I diabetes in children aged 0-14 years in Europe at 3-4 cases per 100,000 person-years. METHODS: We used the sequence specific primer-polymerase chain reaction (PCR-SSP) technique to type HLA-DQB1 alleles, the HLA-DRB1alleles DRB1*03 and one single nucleotide polymorphism (SNP) in the insulin gene (INS). We studied 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 Transmission Disequilibrium Test itself, and the affected family-based control method. RESULTS: We found, as expected, the strong positive DQB1*02-DRB1*03 and DQB1*0302, and negative DQB1*0602, HLA class II allele associations with Type I diabetes in these Romanian families. However, using the affected family-based 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-years in children aged 0-14years). 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 DQB1*02 and DQBI*0302 susceptibility haplotypes in this country.

Type

Journal article

Journal

Diabetologia

Publication Date

10/2001

Volume

44 Suppl 3

Pages

B60 - B66

Keywords

Child, DNA Primers, Diabetes Mellitus, Type 1, Gene Frequency, Genes, MHC Class II, Genotype, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Italy, Nuclear Family, Polymerase Chain Reaction, Risk, Romania