Genotype–phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease

Journal of genetics

B. K. Natesha²  Ganapathy Perumal¹  Sridhar Hebbagodi³  Arindam Maitra¹  Jayashree Shanker1¹  Shibu John³  Vijay V. Kakkar¹  Veena S. Rao² 

[1] Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute, 258/A, Bommasandra Industrial Area, Bangalore 560 099, India$$;Tata Proteomics and Coagulation Unit, Thrombosis Research Institute, 258/A, Bommasandra Industrial Area, Bangalore 560 099, India$$;Elizabeth and Emmanuel Kaye Bioinformatics and Statistics Unit, Thrombosis Research Institute, 258/A, Bommasandra Industrial Area, Bangalore 560 099, India$$

关键词: atherothrombotic phenotype;    CAD;    factor VII.c activity;    R353Q polymorphism;    association;    linkage;    human genetics.;   

DOI  :  

学科分类：生物科学（综合）

来源: Indian Academy of Sciences

【 摘 要 】

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 significantly across R353Q genotype ($P lt 0.0001$). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively ($P lt 0.0001$). 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), respectively, 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.

【 授权许可】

Unknown