04055nas a2200673 4500008004100000022001400041245023000055210006900285260001300354300001100367490000700378520196600385653002502351653001302376653003802389653001102427653004902438653001602487653001702503653002702520100002202547700002402569700002302593700001702616700002002633700002102653700001702674700002102691700002202712700002402734700002402758700001802782700001902800700001702819700002702836700001902863700002002882700001702902700001602919700002702935700002302962700002102985700003203006700002303038700002003061700002603081700003003107700001803137700002403155700002603179700001903205700002003224700001903244700002203263700001703285700002203302700002103324856003603345 2013 eng d a1573-728400aRisk 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.0 aRisk of venous thromboembolism associated with single and combin c2013 Aug a621-470 v283 a
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.
10aCase-Control Studies10aFactor V10aGenetic Predisposition to Disease10aHumans10aMethylenetetrahydrofolate Reductase (NADPH2)10aProthrombin10aRisk Factors10aVenous Thromboembolism1 aSimone, Benedetto1 aDe Stefano, Valerio1 aLeoncini, Emanuele1 aZacho, Jeppe1 aMartinelli, Ida1 aEmmerich, Joseph1 aRossi, Elena1 aFolsom, Aaron, R1 aAlmawi, Wassim, Y1 aScarabin, Pierre, Y1 aHeijer, Martin, den1 aCushman, Mary1 aPenco, Silvana1 aVaya, Amparo1 aAngchaisuksiri, Pantep1 aOkumus, Gulfer1 aGemmati, Donato1 aCima, Simona1 aAkar, Nejat1 aOguzulgen, Kivilcim, I1 aDucros, Véronique1 aLichy, Christoph1 aFernandez-Miranda, Consuelo1 aSzczeklik, Andrzej1 aNieto, José, A1 aTorres, Jose, Domingo1 aLe Cam-Duchez, Véronique1 aIvanov, Petar1 aCantu-Brito, Carlos1 aShmeleva, Veronika, M1 aStegnar, Mojka1 aOgunyemi, Dotun1 aEid, Suhair, S1 aNicolotti, Nicola1 aDe Feo, Emma1 aRicciardi, Walter1 aBoccia, Stefania uhttps://chs-nhlbi.org/node/6007