Effect of the factor VII R353Q missense mutation on plasma apolipoprotein B levels: impact of visceral obesity.
An atherogenic dyslipidemia, characterized by increased plasma triglyceride and apolipoprotein (apo) B levels, low HDL-cholesterol concentrations and the development of small, dense LDL particles has been associated with the presence of abdominal-visceral obesity. Visceral obesity is also associated with a hypercoagulate state and elevated concentrations of procoagulant factors such as factor VII. Moreover, it is known that some genetic variants in the gene encoding factor VII alter its activity and concentration, and consequently these variants may have an impact on atherosclerosis development. The objective of this study was to verify whether the factor VII R353Q polymorphism contributes to predict the risk of an atherogenic dyslipidemia in absence and in the presence of visceral obesity. A sample of 299 French-Canadian men, selected in order to cover a wide range of body fatness values, participated in this study. We observed that the R353 allele was more commonly observed among men characterized by apo B levels below 1.09 g/l than among men with apo B levels greater or above this threshold value (allele frequency of 92.1 vs 85.4%, chi(2)=6.18, P=0.01). Multivariate analyses further showed that the genotype R353/R353 was associated with a lower risk to exhibit atherogenic concentrations of total-apo B (>/=1.09 g/l) and LDL apo B (>/=0.95 g/l) before (odds ratio:0.47, 95%CI=0.27-0.90, P=0.02; odds ratio:0.46, 95%CI=0.25-0.85, P=0.01, respectively) and after adjustments for age and visceral AT (odds ratio:0.49, 95%CI=0.24-0.91, P=0.02; odds ratio:0.44, 95%CI=0.23-0.85, P=0.01, respectively). When the two genotype groups were further divided on the basis of visceral adipose tissue (AT) accumulation using a cutoff point of 130 cm(2), we observed that R353/R353 homozygotes with low visceral AT were characterized by a more favorable lipoprotein-lipid profile, mainly lower total-cholesterol, total-apo B, and LDL-apo B levels compared with R353/R353 homozygotes with high levels of visceral AT. In contrast, irrespective of obesity, plasma lipid levels among carriers of the Q353 allele were similar to those of viscerally obese men homozygous for the R353 allele. In conclusion, results of the present study suggest that the factor VII R353 allele is associated with lower concentrations of plasma apo B levels. However, the presence of visceral obesity abolishes this effect. Further studies will be necessary to confirm this association and the mechanism involved.
Berthier
Marie-Thérèse
MT
Lipid Research Center, CHUQ Pavilion CHUL, 2705 Laurier Blvd, TR93, Sainte-Foy, Quebec, G1V 4G2, Canada.
Houde
Alain
A
Bergeron
Jean
J
Prud'homme
Denis
D
Després
Jean-Pierre
JP
Vohl
Marie-Claude
MC
D000328:Adult; D000483:Alleles; D001055:Apolipoproteins B / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D005167:Factor VII / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk
D001055:Apolipoproteins B; D001786:Blood Glucose; D008078:Cholesterol, LDL; D007328:Insulin; D008074:Lipoproteins; D005167:Factor VII; D002784:Cholesterol