Polymorphisms in folate metabolizing genes and risk for spontaneous preterm and small-for-gestational age birth.
OBJECTIVE
Variants in the folate metabolism pathway affect the accumulation of homocysteine are modified by nutrient levels and have been linked to adverse birth outcomes.


METHODS
We examined the relationship among MTHFR(677), MTHFR(1298), MTR(2756), MTRR(66), and SHMT1(1420), dietary folate intake, and preterm and small-for-gestational-age (SGA) birth in a nested case-control study of black and white women.


RESULTS
White carriers of SHMT1(1420)T or MTRR(66)A had an increased risk of spontaneous preterm birth (odds ratio [OR] = 1.9, 95% CI 1.1-3.1; OR = 2.0, 95% CI 1.1-3.6 respectively). In black women, there appeared to be an interaction between dietary folate intake and the SHMT1(1420)T variant allele, such that only carriers who also were in the lowest quartile of dietary folate intake had higher risk of spontaneous preterm birth (OR = 2.6, 95% CI 0.8-8.0) and SGA (OR = 2.9, 95% CI 0.9-8.9).


CONCLUSIONS
Our results suggest the possibility of a direct or indirect role for the SHMT1(1420)T variant in spontaneous preterm or SGA births.
Engel
Stephanie M
SM
Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Olshan
Andrew F
AF
Siega-Riz
Anna Maria
AM
Savitz
David A
DA
Chanock
Stephen J
SJ
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D044465:White People / Q000235:genetics
D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase