Polymorphisms of ACE and thrombophilic genes: risk for recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) affects up to 5% of pregnancies, but with no consensus on the definition. Inherited thrombophilia has been postulated as a risk factor for RPL. The aim of this study was to investigate the association of RPL with polymorphisms of five genes that influent the coagulation and fibrinolysis. METHODS: This study was conducted on total of 224 women, 129 women with ≥2 early RPL or ≥1 late pregnancy loss, 95 women with at least two normal life births and no history of pregnancy loss. Five gene polymorphisms F2 20 210G>A (rs1799963), F5 1691G>A (rs6025), MTHFR 677C>T (rs1801133), SERPINE1 -675 4G/5G (rs1799762) and ACE I/D (rs1799752) were genotyped by PCR-based methods. RESULTS: A significant relationship was found between SERPINE1 4G/4G and ACE D/D polymorphisms and RPL (p<0.001 both, OR 2.91 and 3.02, respectively). In contrast, no association was found between F2 20 210G>A, F5 1691G>A and MTHFR 677C>T polymorphisms and risk for RPL. A combination of hypofibrinolytic homozygotes SERPINE1 4G/4G+ACE D/D was observed as a highly associated with RPL (Cochran-Armitage test, p<0.001), and their strong independent association with RPL risk was confirmed by logistic regression analysis (both p values <0.001, OR 3.35 and 3.43, respectively). CONCLUSION: Our data have demonstrated that SERPINE1 and ACE gene polymorphisms, individually or in combination, appear to be a significant risk for RPL. This data may be useful in adding to the knowledge on inherited thrombophilia as an important contributor to RPL pathogenesis.

Maternal MTHFR 677C>T, 1298A>C gene polymorphisms and risk of offspring aneuploidy.

OBJECTIVE: The objective was to investigate the association between maternal methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, crucial for DNA methylation, and risk of offspring aneuploidy. METHODS: MTHFR gene polymorphisms 677C>T and 1298A>C were determined by polymerase chain reaction based method, in 163 women with offspring aneuploidy and 155 women with healthy children. Five genetic models were used to assess risk, according to the type of aneuploidy and the age of women at conception. RESULTS: MTHFR 677TT genotype and T allele were significantly more prevalent among women with offspring aneuploidy, with an increased risk of aneuploidy demonstrated under a recessive (OR 3.499), homozygote (OR 3.456) and allele contrast model (OR 1.574). The more prominent association was found with sex chromosome aneuploidies and trisomy 13/18, and also in women ≤35 years at conception. No association was observed between 1298A>C polymorphism and risk of offspring aneuploidy, although synergistic effect of two polymorphisms increase the risk of aneuploidy, primarily amplifying the 677T allele effects (p < 0.001). CONCLUSION: Maternal MTHFR 677C>T gene polymorphism, alone or in combination with another 1298A>C polymorphism, appears to be a substantial risk factor for offspring aneuploidy in Montenegro population, especially for sex chromosome aneuploidies and trisomy 13/18, and among younger women.