title: Genotype-phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease.
abstract: Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed ignificantly across R353Q genotype (P < 0.0001). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively (P < 0.0001). F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score -1.82; P = 0.002). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506-2.850) and 2.472 (95% c.i. = 1.679-3.641), espectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.
authors.affiliation: Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute, 258/A, Bommasandra Industrial Area, Bangalore 560 099, India. jayashreeshanker@triindia.org.in
authors.forename: Jayashree
authors.initials: J
authors.lastname: Shanker
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Perumal
authors.forename: Arindam
authors.initials: A
authors.lastname: Maitra
authors.forename: Veena S
authors.initials: VS
authors.lastname: Rao
authors.forename: B K
authors.initials: BK
authors.lastname: Natesha
authors.forename: Shibu
authors.initials: S
authors.lastname: John
authors.forename: Sridhar
authors.initials: S
authors.lastname: Hebbagodi
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Kakkar
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000941:Antigens / Q000097:blood* / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015415:Biomarkers; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis; D004587:Electrophoresis, Agar Gel; D005167:Factor VII / Q000235:genetics*; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics / Q000473:pathology
chemical_list: D000941:Antigens; D015415:Biomarkers; C042580:factor VII clotting antigen; D005167:Factor VII