Benedetto SimoneValerio De StefanoEmanuele LeonciniJeppe ZachoIda MartinelliJoseph EmmerichElena RossiAaron R. FolsomWassim Y. AlmawiPierre Y. ScarabinMartin Den HeijerMary CushmanSilvana PencoAmparo VayaPantep AngchaisuksiriGulfer OkumusDonato GemmatiSimona CimaNejat AkarKivilcim I. OguzulgenVéronique DucrosChristoph LichyConsuelo Fernandez-MirandaAndrzej SzczeklikJosé A. NietoJose Domingo TorresVéronique Le Cam-DuchezPetar IvanovCarlos Cantu-BritoVeronika M. ShmelevaMojka StegnarDotun OgunyemiSuhair S. EidNicola NicolottiEmma De FeoWalter RicciardiStefania BocciaUniversita Cattolica del Sacro Cuore, RomeAmtssygehuset i HerlevOspedale Maggiore Policlinico MilanoHopital Europeen Georges-PompidouUniversity of Minnesota Twin CitiesArabian Gulf UniversityInsermVU University Medical CenterUniversity of Vermont College of MedicineOspedale Niguarda, MilanHospital Universitari La Fe i Politecnic ValenciaMahidol UniversityIstanbul Tip FakultesiUniversity of FerraraAnkara UniversitesiGazi University, Faculty of MedicineCentre Hospitalier Universitaire de GrenobleKlinikum MemmingenHospital Universitario 12 de OctubreCollegium Medicum Uniwersytet JagiellonskiegoVirgen de la Luz HospitalHospital Universitario San Vicente de PaulGrenoble Universitary HospitalMedical University of PlevenInstituto Nacional de Neurologia y NeurocirugiaRussian Institute of Haematology and Transfusion 2-ndUniverzitetni Klinicni Center LjubljanaMorristown Memorial HospitalKing Hussein Cancer CenterIRCCS San Raffaele Pisana2018-10-192018-10-192013-08-01European Journal of Epidemiology. Vol.28, No.8 (2013), 621-64715737284039329902-s2.0-84884351471https://repository.li.mahidol.ac.th/handle/123456789/32247Genetic 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.Mahidol UniversityMedicineArticleSCOPUS10.1007/s10654-013-9825-8