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

Ionescu-Tîrgoviste, C., Guja, C., Herr, M., Cucca, F., Welsh, K., Bunce, M., Marshall, S.E. and Todd, J.A. (2001) 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. Diabetologia, 44 (S3). B60-B66.

Abstract

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-DRB1 alleles 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 0–14 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 – DQB1*02 and DQB1*0302 susceptibility haplotypes in this country. [Diabetologia (2001) 44 [Suppl 3]: B 60–B 66]