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. 2018 Mar;22(2):78-89.
doi: 10.22034/ibj.22.2.78. Epub 2017 Jul 23.

Association between Thrombophilic Genes Polymorphisms and Recurrent Pregnancy Loss Susceptibility in the Iranian Population: a Systematic Review and Meta-Analysis

Mahdieh Kamali  1   2 , Sedigheh Hantoushzadeh  1 , Sedigheh Borna  2 , Hossein Neamatzadeh  3   4 , Mahta Mazaheri  3   4 , Mahmood Noori-Shadkam  4 , Fatemeh Haghighi  5
Affiliations

Association between Thrombophilic Genes Polymorphisms and Recurrent Pregnancy Loss Susceptibility in the Iranian Population: a Systematic Review and Meta-Analysis

Mahdieh Kamali et al. Iran Biomed J. 2018 Mar.

Abstract

Background: Studies have indicated that thrombophilic genes polymorphisms are associated with recurrent pregnancy loss (RPL) in the Iranian population. However, the results from these studies remained inconsistent and inconclusive. The aim of this systematic review and meta-analysis was to evaluate the precise association between thrombophilic genes polymorphisms (MTHFR C677T, MTHFR A1298C, Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G) and RPL risk in the Iranian population.

Method: Electronic databases of PubMed, Web of Science, Google Scholar, and ISC were searched for eligible articles published up to April 1, 2017. The association between genetic polymorphisms and RPL risk was measured by ORs with 95% CI.

Results: A total of 37 case-control studies in 18 relevant publications were selected in the final meta-analysis, including 1,199 RPL cases and 1,079 controls for MTHFR C677T, 1,194 RPL cases and 1079 controls for MTHFR A1298C, 630 RPL cases and 594 controls for Prothrombin G20210A, 830 RPL cases and 794 controls for FVL G1691A, and 955 RPL cases and 499 controls for PAI-1 4G/5G. When all the eligible studies were pooled into the meta-analysis of MTHFR C677T and A1298C polymorphisms, a significant increased risk of RPL was observed in all genetic models in the population. In addition, Prothrombin G20210A (in allelic and dominant models), FVL G1691A (in allelic and dominant model), and PAI-1 4G/5G (in allelic, homozygote, dominant and recessive genetic models) polymorphisms were associated with RPL risk in the Iranian population.

Conclusion: The findings suggest that the thrombophilic genes polymorphisms are associated with an increased RPL risk in the Iranian population.

Keywords: Recurrent miscarriage; Thrombophilia; Factor V leiden; Prothrombin; Meta-analysis.

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Conflict of interest statement

CONFLICT OF INTEREST. None declared.

Figures

Fig. 1
Fig. 1
Forest plot of RPL susceptibility associated with thrombophilic genes polymorphisms. (A) MTHFR C677T (dominant model: TT + CT vs. CC); (B) MTHFR A1298C (homozygote model; AA vs. CC); (C) Prothrombin G20210A (allele model; A vs. G); (D) FVL G1619A (heterozygote model: GA vs. GG), and (E) PAI-1 4G/5G (dominant model: 4G/4G + 4G/5G vs. 5G/5G). For each study, the estimation of OR and its 95% CI are plotted with a square and a horizontal line. A diamond indicates the pooled OR with 95% CI.
Fig. 2
Fig. 2
Begg’s funnel plots for thrombophilia gene polymorphisms and RPL risk in the Iranian patients to test the publication bias. (A) MTHFR C677T (recessive model: TT vs. CT + CC); (B) MTHFR A1298C (dominant model: AA vs. AC + CC); (C) Prothrombin G20210A (dominant model: AA + GA vs. GG); (D) FVL G1691A (allele model: A vs. G). Each point represents a separate study for the indicated association.
See this image and copyright information in PMC

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