Association between thrombophilic gene variants and thrombosis in the Iranian population: a systematic review and meta-analysis

Thrombophilia is influenced by genetic variants, such as Factor V Leiden (FVL) and the prothrombin G20210A mutation. In clinical settings, assessing numerous genetic factors can lead to diagnostic errors and unnecessary treatments. This meta-analysis examines gene variants associated with thrombosis in the Iranian population, where their role in thrombotic disorders remains underexplored. A systematic literature search was performed across PubMed, Scopus, and Web of Science, targeting case-control studies published up to July 2025. Studies were included if they evaluated thrombophilia-related polymorphisms in Iranian patients with various thrombotic conditions, such as recurrent pregnancy loss (RPL), venous thromboembolism (VTE), or deep vein thrombosis (DVT). Advanced statistical analyses, including random-effects models, fixed-effects models, and Bayesian meta-analysis, were used to compute odds ratios (ORs) and 95% confidence intervals (CIs). From 36 studies encompassing over 14 000 participants, significant associations emerged. For RPL, FVL G1691A heterozygote (OR: 1.998, 95% CI: 1.02-3.88), methylenetetrahydrofolate reductase (MTHFR) C677T heterozygote (OR: 1.77, 95% CI: 1.31-2.39), MTHFR A1298C heterozygote (OR: 3.10, 95% CI: 1.33-7.20) and homozygote (OR: 1.69, 95% CI: 1.05-2.70), prothrombin G20210A heterozygote (OR: 2.435, 95% CI: 1.09-5.39) and homozygote (OR: 0.487, 95% CI: 0.40-0.58), plasminogen activator inhibitor-1 (PAI-1) polymorphisms, factor V (FV) A4070G, FV 5279A/G, factor XIII (FXIII) Val34Leu, and integrin subunit beta-3 (ITGB3)1565T/C were linked to elevated RPL risk. Additionally, FVL G1691A heterozygote (OR: 5.25, 95% CI: 2.39-11.54) was associated with higher VTE risk, while MTHFR C677T heterozygote (OR: 1.404, 95% CI: 1.030-1.914) increased DVT risk. These ethnicity-specific findings highlight critical genetic risk factors for thrombotic disorders in Iranians, potentially guiding precise diagnostics and personalized interventions.

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Across 36 studies and over 14,000 Iranian participants, meta-analysis linked Factor V Leiden heterozygosity to recurrent pregnancy loss (OR 1.998) and venous thromboembolism (OR 5.25), with MTHFR and other variants also associated, potentially guiding ethnicity-specific diagnostics.

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