Response to Endothelial Nitric Oxide Synthase Polymorphisms and Susceptibility to Hypertension: Genotype Versus Haplotype Analysis
In our article,1 we have already reported the importance of haplotypes of endothelial NO synthase (eNOS) gene polymorphisms in association to hypertension. In particular, the paper stated that the overall lack of association between G894T, T786C, and G23T polymorphisms and hypertension, and the discrepancy of results between Whites and East Asians for 4b/a, might be attributable to other unidentified functional mutations that exist in the eNOS gene that affect the susceptibility to hypertension. In addition, the interaction of polymorphisms within haplotypes might be a major determinant of disease susceptibility than the individual polymorphism. Thus, individual eNOS genotypes might not be reliable markers of risk for developing hypertension. A meta-analysis of the combinations of eNOS haplotypes and polymorphisms may provide more reliable information than single polymorphisms. Discrepant results could be because of other loci that may have an effect on the genetic susceptibility to hypertension that are also in linkage disequilibrium with the examined polymorphisms of eNOS gene. Therefore, the comment by Tanus-Santos and Casella-Filho2 does not contradict the conclusions of our meta-analysis. In our case, haplotype-based meta-analysis was not feasible. We believe that a meta-analysis of haplotypes based on a recent published methodology3 could elucidate further the genetics of hypertension. Thus, all investigators will be contacted to provide data on an individual basis in a future study.