Factor VII, blood lipids and fat intake: gene–nutrient interaction and risk of coronary heart disease with the factor VII R353Q polymorphism

Abstract

The relation between dietary fat, blood lipids, plasma factor VII coagulant activity (FVIIc) and risk of coronary heart disease (CHD) according to the R353Q polymorphism in the factor VII gene was assessed. Cross-sectional study of 15,073 individuals participating in the European Prospective Investigation of Cancer (EPIC) Norfolk, 7433 of which had FVIIc available. Nested case-control study of 985 CHD cases and 2009 matched controls. FVIIc was significantly associated with total fat intake in females, especially in the RR homozygotes (standardized beta=0.24; 95% confidence interval (95% CI) 0.08-0.40; P<0.01), but there were no associations with intakes of saturated, monounsaturated or polyunsaturated fatty acids according to genotype and no associations in males. FVIIc was significantly positively associated with total cholesterol (P<0.01) and with triacylglycerol (P<0.001) in both genders, with an interaction according to genotype for triacylglycerol in males: beta Q allele carriers 0.26 (95% CI 0.18-0.34), beta RR homozygotes 0.16 (95% CI 0.12-0.20) (Z interaction=-2.24; P<0.05). There was no effect of genotype on the odds ratio (OR) for incident CHD: OR 0.89 for Q allele carriers compared with RR homozygotes (95% CI 0.77-1.02) in 985 cases and 2009 matched controls. These results show a strong association between dietary fat intake and FVIIc in women, and between serum triacylglycerol and cholesterol and FVIIc levels in both genders. The R353Q genotype only marginally affected modulation of FVIIc by dietary fat. The association between triacylglycerol and FVIIc was significantly stronger in males carrying the Q allele than in those with the RR genotype.