We recently identified rs3918226 as a hypertension susceptibility locus (-665 C>T), TT homozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase (eNOS) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 (P=0.0052) for cardiovascular mortality (4 deaths), 2.75 (P=0.0067) for cardiovascular events (7 endpoints) and 3.10 (P=0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 (P=0.0003), 2.64 (P=0.0091) and 2.89 (P=0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position -665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors.
The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans / L. Olivi, Y.M. Gu, E. Salvi, Y.P. Liu, L. Thijs, D. Velayutham, Y. Jin, L. Jacobs, F. D'Avila, T. Petit, M. Barcella, C. Lanzani, T. Kuznetsova, P. Manunta, C. Barlassina, D. Cusi, J.A. Staessen. - In: JOURNAL OF HUMAN HYPERTENSION. - ISSN 0950-9240. - 29:3(2015), pp. 167-172.
|Titolo:||The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans|
CUSI, DANIELE MARIA (Penultimo)
|Parole Chiave:||nitic-oxide synthase; coronary-artery-disease; blood-pressure; hypertension; population; association; riociguat; target|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
Settore MED/03 - Genetica Medica
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/jhh.2014.66|
|Appare nelle tipologie:||01 - Articolo su periodico|