MTHFR (C677T) polymorphism and PR (PROGINS) mutation as genetic factors for preterm delivery, fetal death and low birth weight: A Northeast Indian population based study

Abstract

Preterm delivery (PTD) is one of the most significant contributors to neonatal mortality, morbidity, and long-term adverse consequences for health; with highest prevalence reported from India. The incidence of PTD is alarmingly very high in Northeast India. The objective of the present study is to evaluate the associative role of MTHFR gene polymorphism and progesterone receptor (PR) gene mutation (PROGINS) in susceptibility to PTD, negative pregnancy outcome and low birth weights (LBW) in Northeast Indian population.

Methods: A total of 209 PTD cases {extreme preterm (< 28 weeks of gestation, n = 22), very preterm (28-32 weeks of gestation, n = 43) and moderate preterm (32-37 weeks of gestation, n = 144) and 194 term delivery cases were studied for MTHFR C677T polymorphism and PR (PROGINS) gene mutation. Statistical analysis was performed using SPSS software.

Results: Distribution of MTHFR and PR mutation was higher in PTD cases. Presence of MTHFR C677T polymorphism was significantly associated and resulted in the increased risk of PTD (p < 0.001), negative pregnancy outcome (p < 0.001) and LBW (p = 0.001); more significantly in extreme and very preterm cases. Presence of PR mutation (PROGINS) also resulted in increased risk of PTD and negative pregnancy outcome; but importantly was found to increase the risk of LBW significantly in case of very preterm (p < 0.001) and moderately preterm (p < 0.001) delivery cases.

Conclusions: Both MTHFR C677T polymorphism and PR (PROGINS) mutation are evident genetic risk factors associated with the susceptibility of PTD, negative pregnancy outcome and LBW. MTHFR C677T may be used as a prognostic marker to stratify subpopulation of pregnancy cases predisposed to PTD; thereby controlling the risks associated with PTD.

Keywords: Low birth weight; MTHFR C677T polymorphism; Negative pregnancy outcome; Northeast India; PR (PROGINS) mutation; Preterm delivery.

Fig. 1

A: Representative photograph of agarose gel electrophoresis for PCR amplification of MTHFR gene fragment. B: Representative photograph of agarose gel electrophoresis of the restriction digestion products of MTHFR gene showing the presence of either wild type or heterozygous (characterized by presence of 198 + 175 + 23 bp and marked by *) or homozygous condition (characterized by the presence of 175 + 23 bp marked by #*) for term and preterm cases. C: Representative photograph of agarose gel electrophoresis showing allele specific PCR amplification of PR gene showing the presence of either wild type (characterized by 170 bp) or heterozygous (characterized by presence of 170 + 306 bp and marked by *) for preterm cases.

Fig. 2

[A]: Box plot analysis showing significant association of MTHFR polymorphism with low birth weight in term (p < 0.001) and extremely preterm (p = 0.006) delivery cases. [B]: Box plot analysis showing significant association of PR mutation with low birth weight in very preterm (p < 0.001) and moderately preterm (p < 0.001) delivery cases.