HLA class II-associated predisposition to insulin-dependent diabetes mellitus in a Polish population.

Susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM) are strongly associated with alleles of HLA class II DR and DQ genes. We have studied HLA DRB1, DQA1, DQB1 allele and haplotype distribution in 152 IDDM children and 103 unrelated healthy individuals from the region of Lodz in central Poland by the polymerase chain reaction and hybridisation with allele-specific oligonucleotide probes. The DRB104 allele showed the strongest association with IDDM in the Polish population (OR = 3.87). The DRB103 allele was also associated with predisposition to the disease (OR = 3.25), particularly in DR3/4 heterozygous individuals (OR = 14.47). Among DR4 subtypes, DRB10401 was the most frequent both in patients and controls, whereas DRB10403 was rarely observed in patients and conferred a significant protection from IDDM. The DRB104-DQA10301-DQB10302 haplotype conferred the highest risk to develop IDDM. The presence of DRB10401 on this haplotype reinforced the disease risk whereas DRB10403 had a dominant protective effect even in the presence of the predisposing DQB10302 allele (OR = 0.24). The DRB11501-DQA10102-DQB10602 haplotype conferred a dominant protective effect (OR = 0.04). The different behaviour of the DRB104-DQB10302 haplotypes in conferring IDDM risk confirms that DRB1 by itself is strongly associated with IDDM independently from DQB1, with DRB10401 being a high frequency/moderate risk allele, and DRB1*0403 a high frequency/low risk allele in the Polish population.