Genetic and environmental determinants of factor VII coagulant activity in ethnic groups at differing risk of coronary heart disease

Abstract

It has been shown previously that individuals possessing the Gln 353 allele of factor VII have significantly lower factor VIIc levels. In this population based study of Europeans, Afro-Caribbeans and Gujarati Indians, the Gln 353 allele was associated with lower factor VIIc in all groups, carriers having factor VIIc levels 20–25% below the group mean. Although the Afro-Caribbeans had the lowest factor VIIc levels, the frequency of the Gln 353 allele was not different from the European sample. However, in the Gujaratis, the frequency of the Gln 353 allele was significantly higher than in the Europeans (0.25 compared to 0.09, P < 0.001). Factor VIIc is known to be positively correlated with plasma triglyceride levels, although the Gujaratis, having the highest mean triglyceride levels, did not have the highest mean factor VIIc levels. On examination of the relationship between triglycerides and factor VIIc in the Gujaratis there was a correlation ( r = 0.23, P = 0.13) in individuals homozygous for the factor VII Arg 353 allele, but no correlation ( r = 0.001, P = 0.5) among Gln 353 carriers. This striking difference suggests that the effect of triglycerides on factor VIIc is genotype specific and thus provides an example of gene-environment interaction. The high frequency of the Gln 353 allele, with its associated lack of relationship between triglyceride and factor VIIc levels, may explain the lower than expected factor VIIc levels in the Gujaratis.