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Racial variation in human leukocyte antigen frequency in insulin-dependent diabetic nephropathy. The South-Eastern
B I Freedman1, M A Espeland, E R Heise
1Department of Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1053.
Insights
Racial disparities in diabetic nephropathy risk are linked to Human Leukocyte Antigen (HLA) genetic differences. Specific HLA types, like HLA-B62 and HLA-DR9, are more common in Black patients, contributing to their higher risk of kidney disease from diabetes.
Area of Science:
- Immunogenetics
- Nephrology
- Medical Genetics
Background:
- Black patients with insulin-dependent diabetes mellitus exhibit a higher incidence of diabetic nephropathy compared to white patients.
- The Human Leukocyte Antigen (HLA) system plays a crucial role in immune responses and has been implicated in various autoimmune and inflammatory conditions.
Purpose of the Study:
- To investigate whether genetic variations in HLA phenotypes contribute to the observed racial differences in the development of diabetic nephropathy among patients with insulin-dependent diabetes mellitus.
Main Methods:
- Analysis of serologically defined HLA phenotypes from a database of renal transplant recipients and donors.
- Comparison of HLA frequencies between Black and white patients with end-stage renal disease (ESRD) due to insulin-dependent diabetes mellitus and race-matched healthy kidney donors.
- Utilized log-linear models and Bonferroni adjustments for statistical analysis.
Main Results:
- Significant racial differences in HLA frequencies were observed beyond typical population variations.
- Black patients showed increased frequencies of HLA-B62 and HLA-DR9 compared to white patients.
- White patients demonstrated decreased frequencies of HLA-A1 and HLA-DR3 compared to Black patients.
Conclusions:
- Differences in HLA antigen frequencies may partially explain the racial disparities in the incidence of diabetic nephropathy.
- Specific HLA associations with diabetic nephropathy were identified within both Black and white populations.
Abstract:
Black patients with insulin-dependent diabetes mellitus are at increased risk for the development of diabetic nephropathy compared with white patients. To determine if genetic differences associated with the HLA system account for racial variation in insulin-dependent diabetes mellitus-induced nephropathy, serologically defined HLA phenotypes from renal transplant recipients and donors in the South-Eastern Organ Procurement Foundation database from 1982 to 1986 were analyzed. Renal transplant recipients (N = 1,531) with insulin-dependent diabetes mellitus-induced renal failure as the cause of ESRD (patients) were compared with 4,506 race-matched, nondiabetic cadaveric kidney donors (controls). Log-linear models were used to assess the relationship between insulin-dependent diabetes mellitus-induced renal failure and prevalence of each HLA phenotype. Bonferroni adjustments of P values were used to correct for multiple comparisons. A comparison of HLA frequencies in patients with insulin-dependent diabetes mellitus-induced renal failure demonstrated the presence of racial differences beyond those normally present between the black and white populations. Blacks, compared with whites, had increased frequencies of HLA-B62 (odds ratio [OR] black:white, 6.13:1.97; P < 0.02) and HLA-DR9 (OR black:white, 4.82:1.57; P < 0.008) and decreased frequencies of HLA-A1 (OR white:black, 1.56:0.8; P < 0.008) and HLA-DR3 (OR white:black, 4.9:2.82; P < 0.004). These results suggest that differences in HLA frequency may account, in part, for the observed racial variation in incidence of diabetic nephropathy. In addition, several antigens in positive and negative association with diabetic nephropathy were identified within each race.