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Updated: Jul 2, 2026

The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo
Published on: August 2, 2017
One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency
Denise L F Furness1, Michael F Fenech, Yee T Khong
1Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia. denise.furness@adelaide.edu.au
Objectives:
This study was undertaken to test novel genetic polymorphisms involved in 1-carbon metabolism for a potential association with increased risk of developing pregnancy complications associated with uteroplacental insufficiency.
Study Design:
This was a prospective cohort study consisting of 50 women at low risk and 93 women at high risk for having a pregnancy complication develop. Maternal and fetal DNA samples were genotyped for methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A. A chi squared or chi(2) analysis was used to compare genotypes and pregnancy outcome, 1-way analysis of variance and linear regression were used to compare genotype with continuous variables.
Results:
The fetal MTR 2756 G allele was associated with uteroplacental insufficiency (P = .022, likelihood ratio = 10.4) and maternal homocysteine (P = .017). The maternal MTR A2756G polymorphism was associated with uteroplacental insufficiency (P = .049, likelihood ratio = 6.0), but only in mothers not supplementing with high-dose B-vitamins. The maternal MTHFD1 AA genotype was associated with intrauterine growth restriction (P = .047, likelihood ratio = 5.8).
Conclusion:
This study suggests the maternal and fetal MTR 2756 G allele is an important risk factor in the development of uteroplacental insufficiency. In addition, the maternal MTHFD1 1958 AA genotype may be associated with intrauterine growth restriction.
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