Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Ribeirao Preto, SP Brazil
* Correspondence to: +55-016-602-3163; Fax: +55-016-633-2301
E-mail address: sabyna{at}usp.br
accepted 12 June 2003
Gorchakova et al. have published a very interesting article addressing the increase in risk of death or myocardial infarction in Caucasian patients that carry the TT genotype for the single nucleotide polymorphism (SNP) 894 G/T in the exon 7 of the endothelial nitric oxide synthase (eNOS) gene within one year of coronary artery stenting.1The authors imply that previous findings indicating functional effects of the SNP 894 G/T (corresponding to a conservative Glu-Asp substitution) could help explain their findings. In this regard, the increased susceptibility to proteolytic cleavage of eNOS with asp298, but not with glu298, would spoil eNOS function. However, there is evidence showing that the previous findings indicating an increased susceptibility to proteolytic cleavage of eNOS with asp298 more likely resulted from sample preparation and cannot explain the increased incidence of cardiovascular disease in carriers of such genetic variant of eNOS gene.2In addition, the authors do not take into consideration that a linkage disequilibrium has been recently demonstrated in Caucasians between the genetic variants in exon 7 and the genetic variants in the promoter region (T-786C) of eNOS gene.3This linkage implies that the rarer variants for both polymorphisms of eNOS gene are transmitted together. Because the occurrence of the rarer variant (C) in the promoter region of eNOS gene suppresses eNOS gene transcription by approximately 50%,4we believe that the SNP in the exon 7 is simply a genetic marker of the unfavourable allele that encodes the eNOS with asp298. Indeed, it was demonstrated in Caucasians that the occurrence of eNOS variants in the promoter region and in the exon 7 decreases platelet derived nitric oxide by approximately 50%5and provides functional evidence of impaired nitric oxide release in carriers of both eNOS genetic variants.
References