Utility of the Arg/Gln polymorphism of the factor VII (FVII) gene, serum lipid levels and body mass index in the prediction of the FVII : C and FVII : Ag in North Karelia; a cross-sectional and prospective study

The arginine/glutamine (Arg/Gln) polymorphism of the factor VII (FVII) gene is associated with variation in coagulation activity (FVII:C) and antigen concentration (FVII:Ag) of the FVII protein. We estimated frequency distrib utions of the Arg and Gln alleles and respective genotypes in North Karelia , and evaluated the utility of this polymorphism, serum lipids, and body ma ss index (BMI) in the prediction of the distributions of FVII:C and FVII:Ag in a cross-sectional study and in a prospective cohort study. The sample c omprised 203 males and 262 females (aged 45-64 years) who were seen twice, in 1992 and 1995. The Arg/Arg genotype and the Arg allele frequencies were among the highest reported so far (86 and 93% respectively, in men; and 89 and 94% respectively, in women). Intragenotypic means of both FVII:C and FV II:Ag were significantly higher in the Arg/Arg genotype than in the Arg/Gln genotype in both genders. Also, intragenotypic variances were different in different genotypes in females. Regression relationships between the FVII: C and FVII:Ag and serum triglyceride, and total cholesterol levels and BMI were positive in both genotypes in both genders, which has not been found i n other populations. In prospective analyses, average changes in the FVII:C and FVII:Ag were genotype specific in both genders, as were also regressio n relationships between these changes and changes in triglyceride level in females (P=0.065 for FVII:C and P=0.061 for FVII:Ag). A consequence of thes e complex genetic architectures is that predictive utility of the Arg/Gln g enotypes depends on population, gender, serum lipid levels, and BMI, and ch anges in these factors over time. (C) 2001 Lippincott Williams & Wilkins.