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.
OBJECTIVE
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).


CONCLUSIONS
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.
Ionescu-Tîrgoviste
C
C
Diabetes Clinic, Institute of Diabetes, Nutrition and Metabolic Diseases N. Paulescu, Bucharest, Romania. nbmetab1@sunu.rnc.ro
Guja
C
C
Herr
M
M
Cucca
E
E
Welsh
K
K
Bunce
M
M
Marshall
S
S
Todd
J A
JA
D002648:Child; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D005787:Gene Frequency; D005802:Genes, MHC Class II; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007558:Italy / Q000453:epidemiology; D009679:Nuclear Family; D016133:Polymerase Chain Reaction; D012306:Risk; D012383:Romania / Q000453:epidemiology
D017931:DNA Primers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains