Author + information
- Jose Eduardo Tanus-Santos, MD, PhD⁎ ( and )
- Antonio Casella-Filho, MD, MSc
- ↵⁎Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil
Rossi et al. (1) reported very interesting and intriguing results of the first prospective study examining the possible effects of 2 single nucleotide polymorphisms (SNP) in the endothelial nitric oxide synthase (eNOS) gene (the T-786C SNP in the promoter region, and the G894T SNP in exon 7) on cardiovascular mortality among high-risk patients. Although no significant effects were found for the G894T SNP, more cardiovascular deaths were found when individuals with TT genotype for the T-786C SNP were compared with CC + CT individuals (1). The significant effect of T-786C SNP on cardiovascular mortality persisted even after many confounding factors were taken into consideration. However, a significant number of individuals (32%) were on lipid-lowering therapy at recruitment (1), and it is probable that an increased proportion of these subjects may have received statins thereafter.
Interestingly, although the T-786C SNP apparently does not significantly affect nitric oxide (NO) availability (2,3), it may modulate the responses to statins. In this regard, we have recently reported that treatment with atorvastatin significantly increased NO availability (measured as whole blood nitrite) in CC individuals, but not in TT individuals (4), thus confirming previous findings suggesting that statins may produce stronger effects on NO availability in CC individuals compared with TT individuals (5). In addition, atorvastatin significantly reduced the concentrations of inflammatory markers in subjects with CC (but not TT) genotype (6). Although these findings derive from studies that included healthy individuals, they suggest that statins may significantly modify the cardiovascular risk associated with the T-786C SNP. Indeed, it is possible that treatment with statins counteracts the effects associated with the T-786C SNP (4), thus leading to apparently paradoxical results such as those reported by Rossi et al. (1).
- American College of Cardiology Foundation
- Rossi G.P.,
- Maiolino G.,
- Zanchetta M.,
- et al.
- Souza-Costa D.C.,
- Sandrim V.C.,
- Lopes L.F.,
- Gerlach R.F.,
- Rego E.M.,
- Tanus-Santos J.E.