Secretory Phospholipase A2-IIA and Cardiovascular Disease : A Mendelian Randomization Study
Articolo
Data di Pubblicazione:
2013
Citazione:
Secretory Phospholipase A2-IIA and Cardiovascular Disease : A Mendelian Randomization Study / M.V. Holmes, T. Simon, H.J. Exeter, L. Folkersen, F.W. Asselbergs, M. Guardiola, J.A. Cooper, J. Palmen, J.A. Hubacek, K.F. Carruthers, B.D. Horne, K.D. Brunisholz, J.L. Mega, E.P.A. van Iperen, M. Li, M. Leusink, S. Trompet, J.J.W. Verschuren, G.K. Hovingh, A. Dehghan, C.P. Nelson, S. Kotti, N. Danchin, M. Scholz, C.L. Haase, D. Rothenbacher, D.I. Swerdlow, K.B. Kuchenbaecker, E. Staines-Urias, A. Goel, F. van 't Hooft, K. Gertow, U. de Faire, A.G. Panayiotou, E. Tremoli, D. Baldassarre, F. Veglia, L.M. Holdt, F. Beutner, R.T. Gansevoort, G.J. Navis, I. Mateo Leach, L.P. Breitling, H. Brenner, J. Thiery, D. Dallmeier, A. Franco-Cereceda, J.M.A. Boer, J.W. Stephens, M.H. Hofker, A. Tedgui, A. Hofman, A.G. Uitterlinden, V. Adamkova, J. Pitha, N.C. Onland-Moret, M.J. Cramer, H.M. Nathoe, W. Spiering, O.H. Klungel, M. Kumari, P.H. Whincup, D.A. Morrow, P.S. Braund, A.S. Hall, A.G. Olsson, P.A. Doevendans, M.D. Trip, M.D. Tobin, A. Hamsten, H. Watkins, W. Koenig, A.N. Nicolaides, D. Teupser, I.N.M. Day, J.F. Carlquist, T.R. Gaunt, I. Ford, N. Sattar, S. Tsimikas, G.G. Schwartz, D.A. Lawlor, R.W. Morris, M.S. Sandhu, R. Poledne, A.H. Maitland-van der Zee, K. Khaw, B.J. Keating, P. van der Harst, J.F. Price, S.R. Mehta, S. Yusuf, J.C.M. Witteman, O.H. Franco, J.W. Jukema, P. de Knijff, A. Tybjaerg-Hansen, D.J. Rader, M. Farrall, N.J. Samani, M. Kivimaki, K.A.A. Fox, S.E. Humphries, J.L. Anderson, S.M. Boekholdt, T.M. Palmer, P. Eriksson, G. Paré, A.D. Hingorani, M.S. Sabatine, Z. Mallat, J.P. Casas, P.J. Talmud. - In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - ISSN 0735-1097. - 62:21(2013 Nov 19), pp. 1966-1976.
Abstract:
BACKGROUND:
Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.
METHODS:
We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.
RESULTS:
PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.
CONCLUSIONS:
Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ACS; CI; LDL-C; MI; MVE; Mendelian randomization; OR; RCT; SNP; acute coronary syndrome(s); cardiovascular diseases; confidence interval; drug development; epidemiology; genetics; low-density lipoprotein cholesterol; major vascular events; myocardial infarction; odds ratio; randomized clinical trial; sPLA(2); secretory phospholipase A(2); single-nucleotide polymorphism
Elenco autori:
M.V. Holmes, T. Simon, H.J. Exeter, L. Folkersen, F.W. Asselbergs, M. Guardiola, J.A. Cooper, J. Palmen, J.A. Hubacek, K.F. Carruthers, B.D. Horne, K.D. Brunisholz, J.L. Mega, E.P.A. van Iperen, M. Li, M. Leusink, S. Trompet, J.J.W. Verschuren, G.K. Hovingh, A. Dehghan, C.P. Nelson, S. Kotti, N. Danchin, M. Scholz, C.L. Haase, D. Rothenbacher, D.I. Swerdlow, K.B. Kuchenbaecker, E. Staines-Urias, A. Goel, F. van 't Hooft, K. Gertow, U. de Faire, A.G. Panayiotou, E. Tremoli, D. Baldassarre, F. Veglia, L.M. Holdt, F. Beutner, R.T. Gansevoort, G.J. Navis, I. Mateo Leach, L.P. Breitling, H. Brenner, J. Thiery, D. Dallmeier, A. Franco-Cereceda, J.M.A. Boer, J.W. Stephens, M.H. Hofker, A. Tedgui, A. Hofman, A.G. Uitterlinden, V. Adamkova, J. Pitha, N.C. Onland-Moret, M.J. Cramer, H.M. Nathoe, W. Spiering, O.H. Klungel, M. Kumari, P.H. Whincup, D.A. Morrow, P.S. Braund, A.S. Hall, A.G. Olsson, P.A. Doevendans, M.D. Trip, M.D. Tobin, A. Hamsten, H. Watkins, W. Koenig, A.N. Nicolaides, D. Teupser, I.N.M. Day, J.F. Carlquist, T.R. Gaunt, I. Ford, N. Sattar, S. Tsimikas, G.G. Schwartz, D.A. Lawlor, R.W. Morris, M.S. Sandhu, R. Poledne, A.H. Maitland-van der Zee, K. Khaw, B.J. Keating, P. van der Harst, J.F. Price, S.R. Mehta, S. Yusuf, J.C.M. Witteman, O.H. Franco, J.W. Jukema, P. de Knijff, A. Tybjaerg-Hansen, D.J. Rader, M. Farrall, N.J. Samani, M. Kivimaki, K.A.A. Fox, S.E. Humphries, J.L. Anderson, S.M. Boekholdt, T.M. Palmer, P. Eriksson, G. Paré, A.D. Hingorani, M.S. Sabatine, Z. Mallat, J.P. Casas, P.J. Talmud
Link alla scheda completa: