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 g enes. We have studied HLA DRB1, DQA1, DQB1 allele and haplotype distri bution 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 DR B104 allele showed the strongest association with IDDM in the Polish population (OR = 3.87). The DRB103 allele was also associated with pr edisposition to the disease (OR = 3.25), particularly in DR3/4 heteroz ygous individuals (OR 14.47). Among DR4 subtypes, DRB10401 was the mo st frequent both in patients and controls, whereas DRB10403 was rarel y observed in patients and conferred a significant protection from IDD M. The DRB104-DQA1*0301-DQB1*0302 haplotype conferred the highest ris k to develop IDDM. The presence of DRB10401 on this haplotype reinfor ced the disease risk whereas DRB10403 had a dominant protective effec t even in the presence of the predisposing DQB10302 allele (OR = 0.24 ). The DRB11501-DQA1*0102-DQB1 *0602 haplotype conferred a dominant p rotective effect (OR = 0.04). The different behaviour of the DRB104-D QB10302 haplotypes in conferring IDDM risk confirms that DRB1 by itse lf is strongly associated with IDDM independently from DQB1, with DRB1 0401 being a high frequency/ moderate risk allele, and DRB1*0403 a hi gh frequency/ low risk allele in che Polish population. Human Immunolo gy 59; 451-455 (1998). (C) American Society for Histocompatibility and Immunogenetics, 1998. Published by Elsevier Science Inc.