One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency.
OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
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.
Furness
Denise L F
DL
Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia. denise.furness@adelaide.edu.au
Fenech
Michael F
MF
Khong
Yee T
YT
Romero
Roberto
R
Dekker
Gustaaf A
GA
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001724:Birth Weight; D002244:Carbon / Q000378:metabolism; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005317:Fetal Growth Retardation / Q000235:genetics; D006801:Humans; D008423:Maternal Age; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D010927:Placental Insufficiency / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D002244:Carbon; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase