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Title: Risk of venous thromboembolism associated with single and combined effects of Factor v Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: A meta-analysis involving over 11,000 cases and 21,000 controls
Authors: Benedetto Simone
Valerio De Stefano
Emanuele Leoncini
Jeppe Zacho
Ida Martinelli
Joseph Emmerich
Elena Rossi
Aaron R. Folsom
Wassim Y. Almawi
Pierre Y. Scarabin
Martin Den Heijer
Mary Cushman
Silvana Penco
Amparo Vaya
Pantep Angchaisuksiri
Gulfer Okumus
Donato Gemmati
Simona Cima
Nejat Akar
Kivilcim I. Oguzulgen
Véronique Ducros
Christoph Lichy
Consuelo Fernandez-Miranda
Andrzej Szczeklik
José A. Nieto
Jose Domingo Torres
Véronique Le Cam-Duchez
Petar Ivanov
Carlos Cantu-Brito
Veronika M. Shmeleva
Mojka Stegnar
Dotun Ogunyemi
Suhair S. Eid
Nicola Nicolotti
Emma De Feo
Walter Ricciardi
Stefania Boccia
Universita Cattolica del Sacro Cuore, Rome
Amtssygehuset i Herlev
Ospedale Maggiore Policlinico Milano
Hopital Europeen Georges-Pompidou
University of Minnesota Twin Cities
Arabian Gulf University
VU University Medical Center
University of Vermont College of Medicine
Ospedale Niguarda, Milan
Hospital Universitari La Fe i Politecnic Valencia
Mahidol University
Istanbul Tip Fakultesi
University of Ferrara
Ankara Universitesi
Gazi University, Faculty of Medicine
Centre Hospitalier Universitaire de Grenoble
Klinikum Memmingen
Hospital Universitario 12 de Octubre
Collegium Medicum Uniwersytet Jagiellonskiego
Virgen de la Luz Hospital
Hospital Universitario San Vicente de Paul
Grenoble Universitary Hospital
Medical University of Pleven
Instituto Nacional de Neurologia y Neurocirugia
Russian Institute of Haematology and Transfusion 2-nd
Univerzitetni Klinicni Center Ljubljana
Morristown Memorial Hospital
King Hussein Cancer Center
IRCCS San Raffaele Pisana
Keywords: Medicine
Issue Date: 1-Aug-2013
Citation: European Journal of Epidemiology. Vol.28, No.8 (2013), 621-647
Abstract: Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought. © 2013 Springer Science+Business Media Dordrecht.
ISSN: 15737284
Appears in Collections:Scopus 2011-2015

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