Increased Frequency of HLA A2/DR4 and A2/DR8 Haplotypes in Young Saskatchewan Aboriginal People with Diabetic End-Stage Renal Disease

Abstract

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 ≤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 HLA.

Association of Selective HLA Class II Susceptibility-Conferring and Protective Haplotypes with Type 2 Diabetes in Patients from Bahrain and Lebanon

“…This was largely due to the larger sample analyzed here (110 patients versus 89 patients). DRB1*040101-DQB1*0302 conferred disease susceptibility in Bahraini patients, in agreement with previous studies on Caucasian (6) and non-Caucasian (8,12) patients, but in disagreement with others which suggested that DR4 was protective (17). This may be due to ethnic background, patient selection, and sample size.…”

Association Between Human Leukocyte Antigen ( HLA ) With Chronic Renal Disease

“…Also in long diabetic patients carrying higher HLA A2 alles have more seriously risk for diabetic nephropathy. [30] Also Freedman et al found higher risk for hypertension in subjects with higher DR3 allele. [31] In our country, a report showed that microalbuminuri risk was higher in tip 1 diabetic patients have higher HLA A2, B8 and A2+B8 alleles.…”

An Association of Maternal Age and Birth Weight with End-Stage Renal Disease in Saskatchewan. Sub-Analysis of Registered Indians and Those with Diabetes

“…Of potentially greater importance for aboriginal peoples experiencing an epidemic of T2DM and DESRD as we have reported in Saskatchewan [32], is the role of excess fetal nutrition rather than fetal deprivation. Although a genetic propensity to develop DESRD (or T2DM) in this population [33]may not be yet amenable to intervention, focusing on the prevention and optimal management of diabetic pregnancies among aboriginal people may provide a partial solution to the epidemic of DESRD.…”