TY - JOUR
T1 - The-665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans
AU - Olivi, L.
AU - Gu, Y-M
AU - Salvi, E.
AU - Liu, Y-P
AU - Thijs, L.
AU - Velayutham, D.
AU - Jin, Y.
AU - Jacobs, L.
AU - D'Avila, F.
AU - Petit, T.
AU - Barcella, M.
AU - Lanzani, C.
AU - Kuznetsova, T.
AU - Manunta, P.
AU - Barlassina, C.
AU - Cusi, D.
AU - Staessen, J. A.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
U2 - 10.1038/jhh.2014.66
DO - 10.1038/jhh.2014.66
M3 - Article
C2 - 25102225
SN - 0950-9240
VL - 29
SP - 167
EP - 172
JO - Journal of Human Hypertension
JF - Journal of Human Hypertension
IS - 3
ER -