Background: Recently, rs3918226 polymorphism in the promoter region of endothelial NO synthase (NOS3) was strongly associated with arterial hypertension in a large genome-wide association study^*. We investigated whether this polymorphism is associated with arterial phenotypes in a Czech general population.

Methods: In a pilot study, we genotyped 101 untreated subjects (age, 54.0 years; 51.5% women, 30.7% smokers). Arterial properties were measured using SphygmoCor. In multivariate-adjusted analyses, we assessed effect of rs3918226 on aortic pulse wave velocity (aPWV) and augmentation index (AIx). As independent covariates we considered sex, age, MAP, heart rate and smoking.

Results: Frequency of rs3918226 genotypes were CC 85.2%, CT 14.8%, and TT 0%. Carriers of mutated T allele tended to have higher both aPWV (8.59±0.45 vs. 7.77±0.18 m/s; P=0.098) and AIx (91.77±3.56 vs. 85.89±1.45%; P=0.13) compared to CC homozygotes. These associations were modified by smoking. In smokers we observed similar trend as in the whole population (0.067<P<0.19), while in nonsmokers we did not find any association (P≥0.50). We did not observe any association between blood pressure and the polymorphism under study (P≥0.67).

Conclusion: This is first study to explore the association of rs3918226 polymorphism in NOS3 gene with arterial properties. We found marginally higher aPWV and AIx in carriers of mutated T allele in this pilot study. We hypothesize that genetic modulation of intermediate arterial phenotypes might lead to higher blood pressure. As the prevalence of T allele is low, further study with sufficient number of subjects is warranted.