@article {6007, 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.}, journal = {Eur J Epidemiol}, volume = {28}, year = {2013}, month = {2013 Aug}, pages = {621-47}, 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.

}, keywords = {Case-Control Studies, Factor V, Genetic Predisposition to Disease, Humans, Methylenetetrahydrofolate Reductase (NADPH2), Prothrombin, Risk Factors, Venous Thromboembolism}, issn = {1573-7284}, doi = {10.1007/s10654-013-9825-8}, author = {Simone, Benedetto and De Stefano, Valerio and Leoncini, Emanuele and Zacho, Jeppe and Martinelli, Ida and Emmerich, Joseph and Rossi, Elena and Folsom, Aaron R and Almawi, Wassim Y and Scarabin, Pierre Y and den Heijer, Martin and Cushman, Mary and Penco, Silvana and Vaya, Amparo and Angchaisuksiri, Pantep and Okumus, Gulfer and Gemmati, Donato and Cima, Simona and Akar, Nejat and Oguzulgen, Kivilcim I and Ducros, V{\'e}ronique and Lichy, Christoph and Fernandez-Miranda, Consuelo and Szczeklik, Andrzej and Nieto, Jos{\'e} A and Torres, Jose Domingo and Le Cam-Duchez, V{\'e}ronique and Ivanov, Petar and Cantu-Brito, Carlos and Shmeleva, Veronika M and Stegnar, Mojka and Ogunyemi, Dotun and Eid, Suhair S and Nicolotti, Nicola and De Feo, Emma and Ricciardi, Walter and Boccia, Stefania} } @article {6542, title = {Association between the metabolic syndrome, its individual components, and unprovoked venous thromboembolism: results of a patient-level meta-analysis.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {34}, year = {2014}, month = {2014 Nov}, pages = {2478-85}, abstract = {

OBJECTIVE: The metabolic syndrome (MetS) may contribute to the pathogenesis of venous thromboembolism (VTE), but this association requires additional investigation.

APPROACH AND RESULTS: We performed a patient-level meta-analysis of case-control and cohort studies that evaluated the role of MetS and risk of unprovoked VTE. For case-control studies, odds ratios and 95\% confidence intervals were calculated using logistic regression analysis to estimate the influence of individual variables on the risk of VTE; χ(2) tests for trend were used to investigate the effect of increasing number of components of MetS on the risk of VTE and to explore the influence of abdominal obesity on this relationship. For cohort studies, hazard ratios and 95\% confidence interval were calculated using multivariable Cox regression analysis. Six case-control studies were included (908 cases with unprovoked VTE and 1794 controls): in multivariate analysis, MetS was independently associated with VTE (odds ratio, 1.91; 95\% confidence interval, 1.57-2.33), and both MetS and abdominal obesity were better predictors of unprovoked VTE than obesity defined by the body mass index. Two prospective cohort studies were included (26,531 subjects and 289 unprovoked VTE events): age, obesity, and abdominal obesity, but not MetS were associated with VTE.

CONCLUSIONS: Case-control but not prospective cohort studies support an association between MetS and VTE. Abdominal adiposity is a strong risk factor for VTE.

}, keywords = {Adult, Aged, Case-Control Studies, Cohort Studies, Female, Humans, Logistic Models, Male, Metabolic Syndrome, Middle Aged, Obesity, Abdominal, Risk Factors, Venous Thromboembolism}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.114.304085}, author = {Ageno, Walter and Di Minno, Matteo N D and Ay, Cihan and Jang, Moon Ju and Hansen, John-Bjarne and Steffen, Lyn M and Vaya, Amparo and Rattazzi, Marcello and Pabinger, Ingrid and Oh, Doyeun and Di Minno, Giovanni and Braekkan, Sigrid K and Cushman, Mary and Bonet, Elena and Pauletto, Paolo and Squizzato, Alessandro and Dentali, Francesco} }