Publication:
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

1

Issued Date

2013-08-01

Resource Type

Article

ISSN

15737284
03932990

DOI

10.1007/s10654-013-9825-8

Other identifier(s)

2-s2.0-84884351471

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Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

European Journal of Epidemiology. Vol.28, No.8 (2013), 621-647

Suggested Citation

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 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. European Journal of Epidemiology. Vol.28, No.8 (2013), 621-647. doi:10.1007/s10654-013-9825-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/32247

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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

Author(s)

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

Other Contributor(s)

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
 Inserm
 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

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.

Keyword(s)

Medicine

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URI

https://repository.li.mahidol.ac.th/handle/123456789/32247

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