Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection

Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FE_NO) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FE_NO levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FE_NO was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aix_ao) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FE_NO and Aix_ao were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FE_NO with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FE_NO and Aix_ao (r = -0.17; 95%CI:-0.32,-0.02). FE_NO showed a significant negative genetic correlation with Aix_ao (r_g = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FE_NO are explained both by genetic and non-shared environmental effects. Covariance between FE_NO and Aix_ao is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.