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Title: The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans
Authors: Olivi, L ×
Gu, Y-M
Salvi, E
Liu, Y-P
Thijs, L
Velayutham, D
Jin, Yu
Jacobs, L
D'Avila, F
Petit, Thibault
Barcella, M
Lanzani, C
Kuznetsova, Tatiana
Manunta, P
Barlassina, C
Cusi, D
Staessen, J A #
Issue Date: Mar-2015
Publisher: Scientific & Medical, Macmillan Press
Series Title: Journal of Human Hypertension vol:29 issue:3 pages:167-72
Article number: 10.1038/jhh.2014.66
Abstract: 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.Journal of Human Hypertension advance online publication, 7 August 2014; doi:10.1038/jhh.2014.66.
ISSN: 0950-9240
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hypertension and Cardiovascular Epidemiology
× corresponding author
# (joint) last author

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