β-Fibrinogen gene G/A-455 polymorphism in relation to fibrinogen concentrations and ischaemic heart disease in Chinese patients with Type II diabetes

Abstract

Aims/hypothesis. We investigated the relation between the G/A-455 (Hae III) β-fibrinogen gene polymorphism and plasma fibrinogen concentration and its role in ischaemic heart disease in 264 Chinese patients with Type II (non-insulin-dependent) diabetes mellitus and 182 non-diabetic control subjects. Methods. The G/A-455 polymorphism was determined in genomic DNA using polymerase chain reaction and Hae III restriction enzyme digestion. Fibrinogen was measured with the Claus method. Results. Fibrinogen concentrations were higher in diabetic patients (3.3±0.5 vs 2.5±0.9 g/l in controls, p < 0.0001) and in women (p < 0.03 vs men). Allele frequency of the variant A allele was 27% in both diabetic patients and control subjects' similar to findings in Caucasians. In control subjects, the AA genotype was associated with higher fibrinogen concentrations (2.8±0.38 g/l vs 2.5±0.5 in GG or GA, p < 0.03), contributing to 4% of the variance in plasma fibrinogen. The genotype effect was smaller and not significant among non- smokers, women and diabetic patients. Higher fibrinogen concentrations and AA genotype frequency were found in diabetic patients with ischaemic heart disease (p < 0.05 and p < 0.005, respectively vs unaffected patients). In a multiple logistic regression model, AA genotype, age and mean arterial pressure were associated with ischaemic heart disease, with odds ratios of 4.19 (p < 0.01), 1.05 (p < 0.0001) and 1.03 (p < 0.03), respectively. Conclusion/interpretation. The G/A-455 polymorphism is a genetic determinant of fibrinogen concentrations and ischaemic heart disease in this Chinese cohort. It also interacts with environmental influences associated with smoking, the female sex and Type II diabetes in determining plasma fibrinogen concentrations.