Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease: A comprehensive systematic-review and meta-analysis

Emanuele Valeriani; Daniele Pastori; Giulia Astorri; Angelo Porfidia; Danilo Menichelli; Pasquale Pignatelli

doi:10.1016/j.thromres.2023.08.006

Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease: A comprehensive systematic-review and meta-analysis

Thromb Res. 2023 Oct:230:74-83. doi: 10.1016/j.thromres.2023.08.006. Epub 2023 Aug 16.

Authors

Emanuele Valeriani¹, Daniele Pastori², Giulia Astorri², Angelo Porfidia³, Danilo Menichelli⁴, Pasquale Pignatelli²

Affiliations

¹ Department of General Surgery and Surgical Specialty, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; Department of Infectious Disease, Umberto I Hospital, Viale del Policlinico 155, Rome, Italy. Electronic address: emauele.valeriani@uniroma1.it.
² Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
³ Department of Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, 00168 Rome, Italy.
⁴ Department of General Surgery and Surgical Specialty, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.

PMID: 37643522
DOI: 10.1016/j.thromres.2023.08.006

Abstract

Introduction: The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients.

Materials and methods: MEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated.

Results: 377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83-4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05-7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02-2.77) and G20210A (heterozygous 1.49 95%CI, 1.22-1.82; homozygous 1.54 95%CI, 0.79-2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80-16.43). Specific subgroups with higher PPs and ORs were identified according to age and region.

Conclusions: Patients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients.

Keywords: Cerebrovascular disorder; Coronary artery disease; Genetic polymorphisms; Peripheral arterial disease; Thrombophilia.