Methylene tetrahydrofolate reductase and methionine synthase gene polymorphisms as genetic determinants of pre-eclampsia.

Abstract

Pre-eclampsia (PE) is a leading cause of maternal and neonatal mortality in Africa; and has been associated with the interplay of genetic, metabolic and environmental factors. Polymorphisms of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) folate cycle genes, have been controversially associated with pre-eclampsia in studies from different human populations. To determine the distribution of MTHFR C677T and MTR A2756G polymorphisms in a Nigerian population and evaluate possible associations with the occurrence of pre-eclampsia and homocysteine metabolic derangement. This study was a hospital based study carried out in Lagos, South-western Nigeria. Two hundred pregnant women clinically diagnosed with pre-eclampsia (study group) and 200 apparently healthy non-pre-eclamptic pregnant women (control group) were recruited for the study after written informed consent. Pre-eclampsia was diagnosed based on the International Society for the Study of Hypertension in Pregnancy re-classification of 2013. MTHFR C677T and MTR A2756G polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analyzes were performed using SPSS version 23. Hardy-Weinberg distribution were tested with χ2 test. Logistic regression model was used to evaluate the relationship of variables with pre-eclampsia. A value of p<0.05 was considered statistically significant. MTHFR genotype frequencies of CC, CT and TT were 59.8%; 31.2% and 9.0% in study group and 76.6%; 22.3% and 1.0% in the control group respectively. MTR A2756G genotype frequencies of AA, AG and GG genotypes were 71.9%; 20.1% and 8.0% for the study group and 81.5%; 16.4% and 2.1% for the control group. Occurrence of pre-eclampsia was significantly associated with presence of T allele of MTHFR (OR=1.855; p<0.05) and G allele of MTR genes (OR=1.269; p<0.05), Homozygosity of TG haplotype significantly increased the occurrence of pre-eclampsia among Nigerian women (OR=2.252; p<0.05). Population attributable risk fraction percent for the T and G alleles were 16.4% and 11.5% respectively. Mean plasma Hcy level was not, however, significantly affected by MTHFR/MTR haplotypes (F=1.54; p=0.157). MTHFR C677T and MTR A2756G polymorphisms were associated with pre-eclampsia in a population of pregnant women in Lagos, Nigeria.