The association between plasma fibrinogen levels, fibrinogen genotype, and the development of macrovascular disease was studied in 100 patients with non-insulin dependent diabetes mellitus (NIDDM). The mean plasma fibrinogen levels in patients with macrovascular disease was higher than those without, although the difference was not statistically significant (3.67 g l-1, and 3.43 g l-1, respectively). The frequency of the rare allele of the fibrinogen gene DNA polymorphism detected with the restriction enzyme Bc1I was slightly higher in the group of patients with disease, but the difference was not statistically significant (0.20 vs 0.16). The frequency of the TaqI polymorphism rare allele was the same in both groups (0.30 vs 0.31). However, the Bc1I polymorphism was strongly associated with plasma fibrinogen levels, with those patients heterozygous for the rare allele having mean levels 16 per cent higher than those lacking the allele (3.81 g l-1 vs 3.28 g l-1, p < 0.05). This data demonstrates that variation at the fibrinogen locus is involved in determining fibrinogen levels in patients with NIDDM, and suggests the possibility that fibrinogen genotype and plasma fibrinogen levels could be one of the factors making a small contribution to the development of macrovascular disease in diabetic patients.

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