Increased frequency of HLA A2/DR4 and A2/DR8 haplotypes in young Saskatchewan aboriginal people with diabetic end-stage renal disease

Aims: To determine the association of HLA with diabetic end-stage renal disease (DESRD) in Saskatchewan aboriginal people. Methods: This was a retrospective study of HLA profiles in four groups of Saskatchewan residents with ESRD diagnosed from 1980 to 1998: aboriginal people with and without DESRD, and non-aboriginal people with and without DESRD. The aboriginal DESRD group was also subdivided into those less than or equal to 50 and > 50 years of age. Frequencies of individual and combinations of HLA antigens were compared between groups and subgroups. Results: HLA data were available for 634 subjects. Young aboriginal people with DESRD had a higher frequency of HLA-A2 than older AB DESRD subjects (69 vs. 36%; p = 0.03), and of HLA-DR4 and/or DR8 compared to older AB DESRD subjects (91 vs. 68%; p = 0.07) and AB non-DESRD subjects (91 vs. 67%; p = 0.03). Over 65% of young AB DESRD subjects had either an A2/DR4 or A2/ DR8 haplotype (odds ratio 5.09 [confidence intervals 1.35, 20.15] versus older AB DESRD subjects; odds ratio 3.32 [confidence intervals 1.20, 9.3] versus AB non-DESRD subjects). Forty percent of young AB DESRD subjects were homozygous for at least one of A2, DR4 or DR8. Conclusions: Our findings suggest that DESRD in young AB subjects with T2DM has a genetic basis related to H LA. Copyright (C) 2003 S. Karger AG, Basel.