Increased homocysteine expression associated with genetic changes in the folate pathway as a key determinant of preeclampsia: A prospective study from lower Assam, India

Abstract

Lacunae exist in the scientific understanding of preeclampsia (PE) pathogenesis, which is a global issue and a clinical challenge during pregnancy and contributes to both maternal and fetal morbidity and mortality. We aim to understand the significance of homocysteine levels and folate pathway parameters in PE pathogenesis involving pregnancy cases from lower Assam, India. PE cases {N = 145, mild-PE (n = 108), severe-PE (n = 37)} and 192 normal full-term delivery cases were evaluated for Hcy expression and Vitamin B12 levels and evaluated for association with MTHFR and TYMS polymorphisms in PE pathogenesis. Hcy level was significantly higher in PE cases with negative pregnancy outcomes (p = 0.003) and was higher in PE-preterm delivery compared to PE-term delivery cases (p = 0.301). The VitaminB12 levels were not associated with higher tHcy concentration. Distribution of MTHFRC677T variant genotype was significantly higher in severe-PE cases compared to mild-PE cases (p = 0.050) and was associated with an increased risk of severe PE. The combined variant genotype of MTHFR and TYMSdel6 polymorphism resulted in significant increase (p = 0.014) in the risk of severe-PE compared to mild-PE. Within the PE delivery group, the combined variant genotypes showed association with higher homocysteine levels both in live birth cases as well in the PE cases with negative pregnancy outcomes. Increased homocysteine levels were associated with combined variant genotypes and were consistent in both term and preterm delivery in PE cases. The study points out the prognostic significance of MTHFR C677T, TYMS 1494del6 genotype and tHcy levels as a risk factor for PE, negative pregnancy outcome and preterm delivery.