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Is diabetic microangiopathy genetically heterogeneous? HLA and diabetic nephropathy
Insights
Human Leukocyte Antigen (HLA) B8, B15, and B18 antigen frequencies were elevated in insulin-dependent diabetics with and without kidney disease. These findings in diabetic nephropathy differ from those in diabetic retinopathy.
Area of Science:
- Immunogenetics
- Endocrinology
- Nephrology
Background:
- Insulin-dependent diabetes mellitus (IDDM) is associated with microvascular complications.
- Diabetic nephropathy and retinopathy are significant microvascular complications.
- Human Leukocyte Antigen (HLA) associations with diabetic complications are not fully understood.
Purpose of the Study:
- To investigate the association of HLA antigens A and B with diabetic nephropathy.
- To compare HLA antigen frequencies in IDDM patients with and without kidney disease.
Main Methods:
- Case-control study design.
- Analysis of HLA-A and HLA-B antigen frequencies in 99 IDDM patients with terminal uremia and 96 IDDM patients without kidney disease.
- Matching of groups for disease duration and clinical features.
Main Results:
- Significantly increased frequencies of HLA antigens B8, B15, B18, and the B8/B15 haplotype were observed in both diabetic groups.
- Significantly decreased frequencies of HLA antigens B7 and B12 were noted in both groups.
- No significant differences in HLA antigen frequencies were found between diabetic patients with and without kidney disease.
Conclusions:
- The study suggests a potential genetic predisposition related to specific HLA antigens in insulin-dependent diabetes.
- Observed HLA associations with diabetic nephropathy differ from those reported for diabetic retinopathy, indicating potential distinct genetic underpinnings for these microvascular complications.
- Differences may stem from sample bias or genuine genetic variations between types of diabetic microangiopathy.
Abstract:
We have studied the histocompatibility (HLA) antigens A and B in 99 insulin dependent diabetics (IDDN) with terminal uremia due to diabetic nephropathy and in 96 insulin dependent diabetic patients (IDD) without clinically detectable kidney disease. The two groups were matched for duration of disease and other clinical features. The frequencies of the HLA antigens B8, B15, B18 and B8/B15 were significantly increased in both groups and B7 and B12 were decreased. There were no significant differences between the two groups. These results contrast with previously described similar studies of HLA and diabetic proliferative retinopathy. In these studies B7 was significantly less common in patients with proliferative retinopathy as compared with patients without proliferative retinopathy and B15 was more common in a subset of patients with proliferative retinopathy. The differences between the two studies may reflect sample bias or a genetic difference between the two types of diabetic microangiopathy.