Journal Article

The −665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans

Olivi, L, Jacobs, L, Kuznetsova, T, Cusi, D, Gu, Y-M, D'Avila, F, Lanzani, C, Velayutham, D, Barlassina, C, Staessen, J A, Petit, T, Jin, Y, Salvi, E, Thijs, L, Liu, Y-P, Barcella, M, Manunta, P

2015

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/457/649 / 692/53/2423 / 692/699/75/243 / Adult / Alleles / Antihypertensives / Belgium - epidemiology / Blood pressure / Cardiovascular diseases / Cardiovascular Diseases - genetics / Cardiovascular Diseases - mortality / Epidemiology / European Continental Ancestry Group - genetics / Female / Gene polymorphism / Health Administration / Health risk assessment / Homozygotes / Humans / Hypertension / Male / Medicine / Medicine & Public Health / Middle Aged / Morbidity / Mortality / Nitric Oxide Synthase Type III - genetics / Nitric-oxide synthase / original-article / Polymorphism, Single Nucleotide / Public Health / Risk factors / Susceptibility / Young Adult