A controversial relationship was reported between the polymorphisms within the coagulation factor VII gene and CHD in different populations, including previous meta-analyses, led us to conduct the present study.
Wu et al. conducted a meta-analysis and reported that the combined RQ and QQ genotype of factor VII R353Q was correlated to a reduced risk for cardiovascular disease in 2,574 patients (OR 0.78, 95% CI 0.65 to 0.93), whereas the QQ genotype had offered more protection (OR 0.53, 95% CI 0.27 to 1.03). However, the combined analyses result reported by Ye and coworkers , among 24 available studies with a total of 7,444 patients and 12,110 control individuals, showed no significant overall associations with CHD, yielding per-allele relative risks (RR) of 0.97 (95% CI 0.91 to 1.04). Our study showed the significant association between R353Q polymorphism and CHD in Asian population. The most noteworthy findings of this meta-analysis were that the 353QQ+QR genotype and 353Q allele consistently appeared to be significantly associated with a reduced risk of CHD. Our result for the overall population supported that of the recent meta-analysis conducted by Ye and coworkers. We found five studies reported after 2006, when Ye et al. conducted their meta-analysis, and we reviewed these studies in our study. In cumulative analysis we found significant overall associations between the R353Q polymorphism and the risk for CHD only after the study published by Huang et al.  was included. Nevertheless, we still failed to find significant associations for European and other populations.
For the -323Ins10 polymorphism, the A2 allele was observed to be a protective effect in both Asian and European individuals, without publication bias and significant heterogeneity. The A2A2+A2A1 genotype and A2 allele consistently appeared to be significantly associated with a reduced risk of CHD. For the HVR4 polymorphism, we also found a protective effect in Asian individuals, although the odds ratio failed to reach statistical significance in European population. The study samples for the -323Ins10 and HVR4 polymorphism were still small, further large case-control studies are needed for these two polymorphisms.
According to our results, the association between F7 polymorphisms and CHD risk may be different in different ethnicities. Significant association was only found in East Asian population for the R353Q polymorphism in our meta-analysis. We found no significant associations in the Europeans, this result was consistent with the study of CARDIoGRAM consortium (by corresponding to authors). The -323Ins10 polymorphism was significantly associated with CHD risk in both European and East Asian populations. Lack of association was found for HVR4 polymorphism both in European and East Asian populations.
Several potential limitations of our study should be noted. First, we should realize that the results might be distorted by potential weakness and biases of genetic association studies, such as genotyping error, phenotype misclassification, population stratification, gene-gene or gene-environment interactive effect, and selective reporting biases [25, 35]. Second, although no statistically significant publication bias was found from Egger's test, exclusion of unpublished studies may affect the validity of the analysis. The eligible studies in our research were mainly from Asia and Europe, data of other populations, like African, was limited. Third, because we did not have access to individual data, we could not control for population stratification, nor could we adjust for variables in possible intermediate pathways.
The exact biological role of the particular polymorphism remains to be determined. In theory, FVII contribute to atherosclerosis through the generation of thrombin and fibrin formation. Development of coagulation in the vessel wall may result in production of thrombin and activation of platelet, leading to the release of various cytokines and the proliferation of smooth muscle cells in the vessel wall. Thus, someone with a lower FVIIc level may have less chance of developing CAD. Moreover, thrombin can have pro-inflammatory properties and pro-angiogenic activities. Vascular tone, inflammation, blood viscosity, and angiogenesis can play roles in initiating and maintaining an elevation in BP and, therefore, are potential mechanisms contributing to the association between FACTOR VII and risk factors like smoking, diabetes, hypertension, and mental stress. The FVII polymorphisms were reported to be associated with decreased blood pressure and a decreased risk of hypertension , suggesting that these FVII variants might influence cardiovascular risk through mechanisms other than thrombosis.
Further studies which aim to confirm the functional variants should be needed. More studies are needed to elucidate the complete range of the signal transduction pathways that the variant is implicated in, and thus, throw light in the underlying molecular mechanisms that confer susceptibility to CHD. The particular polymorphism associated with CHD itself may not play a functional role, but rather it may be located physically close to the actual disease-predisposing gene.
In addition to the genetic markers described in this analysis, many other polymorphisms in genes encoding important biochemical or coagulation factors have been studied. Those polymorphisms may be candidates for a multivariate analysis. Future haplotypic approaches and further haplotype-based meta-analyses will provide more powerful and informative results than current single genotype-based data.