Diabetes mellitus, atherosclerosis, and the 5' flanking polymorphism of the human insulin gene.

On the 5' side of the human insulin gene is a highly polymorphic locus containing 2 major size classes of DNA restriction fragments which segregate in families as stable genetic elements. Fragments with an average size of about 600 base-pairs (bp) (the 'L-allele') seem to be a weak genetic marker for type 1 (insulin-dependent) diabetes mellitus, whereas fragments of an average size of about 2500 bp (the 'U-allele') have hitherto been associated with type 2 (non-insulin-dependent) diabetes mellitus and diabetic hypertriglyceridaemia. Recent evidence does not confirm the association between the U-allele and type 2 diabetes. Our own studies suggest that the U-allele is a fairly strong marker for the development of atherosclerosis with a relative risk for U-carriers of 3.36. The U-allele has not been associated with conventional cardiovascular risk factors such as body weight, blood pressure, or levels of blood glucose, triglycerides or lipoproteins. The putative functions of the polymorphic region in the aetiology of type 1 diabetes and atherosclerosis, and the relation of this region to other genetic markers for these disorders are not known.