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

Airns/hypothesis. We investigated the relation between the G/A-455 (Hae III ) beta-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 subje cts. Methods. The G/A-455 polymorphism was determined in genomic DNA using polym erase chain reaction and Hae III restriction enzyme digestion. Fibrinogen w as 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 pa tients and control subjects' similar to findings in Caucasians. In control subjects, the AA genotype was associated with higher fibrinogen concentrati ons (2.8 +/- 0.38 g/l vs 2.5 +/- 0.5 in GG or GA, p < 0.03), contributing t o 4% of the variance in plas-ma 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, respectivel y vs unaffected patients). In a multiple logistic regression model, AA geno type, age and mean arterial pressure were associated with ischaemic heart d isease, 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 determinan t of fibrinogen concentrations and ischaemic heart disease in this Chinese cohort. It also interacts with environmental influences associated with smo king, the female sex and Type II diabetes in determining plasma fibrinogen concentrations.