Genetic variants in MTHFR and PAI-1 genes and their influence on miscarriage risk in the Iranian population

Introduction

Spontaneous abortion is a multifactorial condition, with genetic polymorphisms being one of the proposed contributing factors. This study aimed to evaluate the association between MTHFR A1298C, MTHFR C677T, and PAI-1 gene polymorphisms and spontaneous abortion.

Materials and methods

This case-control study included women with history of abortion as case group and a similar group with the same size as healthy controls. Genotype distributions of MTHFR A1298C, MTHFR C677T, and PAI were determined using sanger sequencing technique. Statistical analyses included chi-square tests to compare genotype distributions and logistic regression to assess the predictive value of these polymorphisms on abortion outcomes were considered and generalized linear model evaluated the impact of genotypes on the number of abortions.

Results

Total number of 250 women included in the case group with the mean age of 31 ± 6.5 years. Significant differences in genotype distributions were observed for MTHFR A1298C (p = 0.037) and PAI (p = 0.001) between case and control groups, suggesting their association with pregnancy loss. However, MTHFR C677T showed only a marginal association (p = 0.062). Despite these differences, regression analysis revealed no significant effects of these genotypes on the likelihood or number of abortions (p > 0.05). Generalized linear model analysis also confirmed no significant contributions of these polymorphisms to abortion outcomes.

Conclusion

While MTHFR A1298C and PAI polymorphisms are associated with pregnancy loss, their independent predictive value appears limited. These findings underscore the complex, multifactorial nature of pregnancy loss and highlight the need for further research to explore gene-gene and gene-environment interactions in understanding its etiology.