Genetic variation of a collagen IV alpha 1-chain gene polymorphism in Danish insulin-dependent diabetes mellitus (IDDM) patients: lack of association to nephropathy and proliferative retinopathy

In insulin-dependent (Type 1) diabetes mellitus (IDDM) the development of nephropathy is partly due to genetic susceptibility. Previously one study has demonstrated a relationship between a HindIII restriction polymorphism of the collagen IV alpha 1-chain gene and diabetic nephropathy. The aim of the present study was to evaluate such as association in a case-control study including 207 Danish IDDM patients: 116 with nephropathy (urinary albumin excretion rate (AER) > 300 mg 24 h-1) and 91 without nephropathy (AER < 30 mg 24 h-1). Using genomic DNA, HindIII restriction fragment length analysis revealed a bi allele polymorphism visualized by southern hybridization with a cDNA probe recognizing the collagen IV alpha 1-chain gene. No differences in genotype frequencies or allele frequencies were demonstrated comparing patients with and without nephropathy: p = 0.39 and p = 0.96, respectively. Neither were there any difference in genotype frequencies or allele frequencies when the patients were stratified according to the presence of proliferative retinopathy: p = 0.44 and p = 0.84, respectively. Pooling the diabetic groups revealed genotype frequencies and allele frequencies comparable to those found in 57 healthy unrelated Danish individuals. We conclude that in a Danish IDDM population a HindIII restriction polymorphism of the collagen IV alpha 1-chain gene is not associated with diabetic nephropathy, diabetic retinopathy or with diabetes per se.