Influence of the Enos Gene Polymorphisms on the Homocysteine Plasma Levels in Healthy Subjects

Abstract number: P1684A

Sofi¹ F, Fatini¹ C, Sticchi¹ E, Gori¹ AM, Filoni¹ C, Baldi¹ M, Casini² A, Surrenti² C, Gensini¹ GF, Abbate¹ R

¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ²²Department of Clinical Pathophysiology, Unit of Clinical Nutrition, University of Florence, Italy

Nitric oxide (NO) plays a relevant role in various events during atherogenesis. In vitro data suggested that NO may modulate plasma homocysteine (Hcy). Aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) T-786C, G894T and 4a/4b polymorphisms in influencing Hcy plasma levels. Blood samples were obtained from 1287 unrelated subjects. Hcy plasma levels were determined by fluorimetric polaryzed immuno assay, folate and vitamin B12 levels by radio immuno assay, vitamin B6 by high performance liquid chromatographic assay and eNOS and MTHFR polymorphisms by polymerase chain reaction – restriction fragment length polymorphism analysis. MTHFR C677T polymorphism significantly influenced Hcy levels after adjustment for all confounding variables (Pfor trend < 0.0001). Univariate analysis showed that eNOS T-786C but not G894T and 4a4b polymorphism was significantly associated with the risk of having Hcy in the 3^rd tertile (>13.4 µmol/L) (OR: 1.2 95% CI 1.02–1.5; P= 0.03). After adjustment for all variables known to influence Hcy levels, T-786C polymorphism still remains to influence Hcy levels (OR: 1.9 95% CI 1.1–3.2; P= 0.01). By analysing the influence of eNOS polymorphisms on Hcy plasma levels according to vitamin levels (folate, vitamin B6 and vitamin B12), age (<60 yrs), and smoking habit we showed a significant association between the eNOS T-786C polymorphisms and Hcy levels in non smoker subjects with normal vitamin status, aged less than 60 yrs. In conclusion, we documented that eNOS T-786C, but not G894T and 4a4b polymorphisms, mildly but significantly influences Hcy plasma levels.