INCREASED AND DECREASED RELATIVE RISK FOR NONINSULIN-DEPENDENT DIABETES-MELLITUS CONFERRED BY HLA CLASS-II AND BY CD4 ALLELES

Non-insulin-dependent diabetes mellitus has been recognized to be hete rogeneous in etiology, with multiple subgroups. Several genes or chrom osomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes a nd the association of CD4 and CD3 polymorphisms were assessed in a lar ge number of Belgian non-insulin-dependent diabetes mellitus patients. Furthermore, the importance of the DQ alpha 1(Arg52)/DQ alpha 1(Arg52 ) and the DQ beta 1(Asp57)/DQ beta 1(Asp57) genotypes and the combinat ion of both genotypes were examined. Our results show that in the HLA class-II genes only the DQ alpha 1(Arg52)+/DQ alpha 1(Arg52+) genotype was significantly associated with noninsulin-dependent diabetes melli tus compared with controls (p=0.011, RR=2.02). We also observed that t he frequency of the CD4()A4/(*)A8 genotype and the CD4(*)A7 allele wa s significantly increased and decreased respectively in non-insulin-de pendent diabetes mellitus patients as compared with the controls (p=0. 018, RR=2.16 and p=0.0003, RR=0.49 respectively). These results theref ore suggest that HLA class II and CD4 genes might independently contri bute to the susceptibility for non-insulin-dependent diabetes mellitus and that these alleles and genotypes might identify subgroups of pati ents with different susceptibilities.