Shanker Jayashree, Perumal Ganapathy, Maitra Arindam, Rao Veena S, Natesha B K, John Shibu, Hebbagodi Sridhar, Kakkar Vijay V
Mary and Garry Weston Functional Genomics Unit, Thrombosis Research Institute, 258/A, Bommasandra Industrial Area, Bangalore 560 099, India.
J Genet. 2009 Dec;88(3):291-7. doi: 10.1007/s12041-009-0042-x.
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.
凝血因子VII（FVII）水平升高是冠状动脉疾病（CAD）的一个危险因素。我们在139个患有CAD的印度家庭中研究了F7基因中R353Q多态性的作用，这些家庭包括222名患病个体、105名未患病个体和126对患病同胞对。不同R353Q基因型的血浆FVIIc活性百分比（FVII.c活性）差异显著（P < 0.0001）。RR和QQ基因型个体的频率分别在FVII.c活性的第4四分位数和第1四分位数中较高（P < 0.0001）。通过回归分析，F7 R353Q单核苷酸多态性（SNP）能够解释FVII.c活性高达7%的变异，通过遗传力分析，加性遗传成分的方差为28.04%。数量性状位点分析显示F7 SNP与FVII.c活性百分比有提示性的连锁证据（LOD分数为 -1.82；P = 0.002）。RR和RQ基因型个体患CAD风险的比值比（OR）分别为2.071（95%置信区间 = 1.506 - 2.850）和2.472（95%置信区间 = 1.679 - 3.641）。在协变量调整后，FVII.c活性与脂质标志物有显著相关性，特别是在RR和RQ基因型个体中。总之，F7 R353Q SNP似乎对印度人的血浆FVII.c活性和CAD风险有中度影响。
