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*

*Corresponding author for this work

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7 Citations (Web of Science)


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.
Original languageEnglish
Pages (from-to)167-172
JournalJournal of Human Hypertension
Issue number3
Publication statusPublished - Mar 2015

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