Interaction between Polymorphisms MTHFR C677T and MTRR A66G and Vitamin Levels in Pregnant Women.
Authors: Guerra-Shinohara Elvira M. , Barbosa Patricia R. , Sampaio-Neto Luiz F. , Hirata Rosario D. , Hirata Mario H. , Allen Robert H. , Stabler Sally P. 
Published: October 2019

In the homocysteine metabolic pathway, several key enzymes, including methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have been implicated in abnormal homocysteine accumulation in the presence of rare alleles. In previous study, we showed that lower maternal Cbl levels were associated with higher tHcy and lower S-adenosylmethionine/S-adenosylhomocysteine ratio in pregnant women and their neonates.The aim of this study is to investigate whether MTHFR and MTRR polymorphisms are involved in the risk for elevated total homocysteine (tHcy) and its interaction with low cobalamin (Cbl) or serum folate (SF) levels. Genotypes for polymorphisms MTHFR C677T and MTRR A66G were determined by PCR-FLRP. The serum levels of Cbl, SF and tHcy were determined in 377 pregnant women (37–42 weeks of gestational age), and cutoff values for Cbl and SF were considered the first quartile (low values). Four models of univariate logistic regression analyses were used (Table 1). Pregnant women with MTHFR 677T allele have high risk for elevated tHcy that is increased when 677T allele is associated with low Cbl. Increased risk for elevated tHcy is also met when MTRR 66G allele and low Cbl levels were associated. Women with low SF and common MTHFR and MTRR alleles have high risk for elevated tHcy, that is increased when in association with 677T allele or with 66G allele.

Interaction between MTHFR C677T and MTRR A66G polymorphisms and vitamins levels in pregnant women

Dependent variables Comparation levels (N) P value Odd Ratios 95% CI P for trend: (a) P<0.001; (b) P<0.001; (c) P=0.067; (d) P<0.001 tHcy>8.3μmol/L MTHFR 677CC genotype and Cbl> 115.8 pmol/L (ref) (136) a 1.00 MTHFR 677CC genotype and≤Cbl 115.8 pmol/L (45) 0.298 1.57 0.67 – 3.63 MTHFR 677CT and 677TT genotypes and Cbl>115.8 pmol/L (145) 0.015 2.09 1.16 – 3.77 MTHFR 677CT and 677TT genotypes and≤Cbl 115.8 pmol/L (48) 0.001 4.63 2.22 – 9.65 tHcy>8.3μmol/L MTHFR 677CC genotype and SF > 10.9 nmol/L (ref) (148) b 1.00 MTHFR 677CC genotype and≤SF 10.9 nmol/L (33) 0.008 3.20 1.35 – 7.59 MTHFR 677CT and 677TT genotypes and SF > 10.9 nmol/L (133) 0.035 1.95 1.05 – 3.61 MTHFR 677CT and 677TT genotypes and≤SF 10.9 nmol/L (59) 0.001 6.62 3.31 – 13.26 tHcy>8.3μmol/L MTRR 66AA genotype and Cbl> 115.8 pmol/L (ref) (96) c 1.00 MTRR 66AA genotype and ≤Cbl 115.8 pmol/L (23) 0.222 1.90 0.68 – 5.29 MTRR 66AG and 66GG genotypes and Cbl>115.8 pmol/L (183) 0.418 1.29 0.70 – 2.39 MTRR 66AG and 66GG genotypes and ≤Cbl 115.8 pmol/L (69) 0.013 2.46 1.21 – 5.01 tHcy>8.3μmol/L MTRR 66AA genotype and SF > 10.9 nmol/L (ref) (92) d 1.00 MTRR 66AA genotype and ≤SF 10.9 nmol/L (27) 0.006 3.83 1.47 – 9.96 MTRR 66AG and 66GG genotypes and SF > 10.9 nmol/L (186) 0.399 1.34 0.68 – 2.63 MTRR 66AG and 66GG genotypes and≤SF 10.9 nmol/L (65) 0.001 4.78 2.26 – 10.10

In conclusion, the interaction between MTHFR and MTRR polymorphisms and low folate and cobalamin serum levels may explain the increased risk for elevated tHcy found in pregnant women.