Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery.
BACKGROUND
Folate is critical for cell division, a major feature of in utero development. Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell.


OBJECTIVE
We aimed to determine whether a common, recently discovered deletion polymorphism in the DHFR gene is a risk factor for preterm delivery or low birth weight.


METHODS
We studied 324 pregnant women from Camden, NJ. Folate intake was computed from folate supplement intake plus the mean of two 24-h recalls completed during the course of pregnancy. Genomic DNA was extracted from the women's leukocytes and genotyped.


RESULTS
Women with a deletion allele had a significantly greater risk of preterm delivery [adjusted odds ratio (AOR): 3.0; 95% CI: 1.0, 8.8; P < 0.05] than did those without a deletion allele. Women with both a DHFR deletion allele and low folate intake (<400 microg/d from diet plus supplements) had a significantly greater risk of preterm delivery (AOR: 5.5; 95% CI: 1.5, 20.4; P = 0.01) and a significantly greater risk of having an infant with a low birth weight (AOR: 8.3; 95% CI: 1.8, 38.6; P = 0.01) than did women without a deletion allele and with a folate intake >/=400 microg/d.


CONCLUSIONS
The DHFR 19-base pair deletion allele may be a risk factor for preterm delivery. In the presence of low dietary folate, the allele may also be a risk factor for low birth weight. This may be a gene-environment interaction.
Johnson
William G
WG
Department of Neurology, University of Medicine and Dentistry New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA. wjohnson@umdnj.edu
Scholl
Theresa O
TO
Spychala
John R
JR
Buyske
Steven
S
Stenroos
Edward S
ES
Chen
Xinhua
X
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015331:Cohort Studies; D016001:Confidence Intervals; D036861:Delivery, Obstetric; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007962:Leukocytes; D019656:Loss of Heterozygosity; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology* / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D017384:Sequence Deletion; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D013940:Thymidylate Synthase / Q000378:metabolism
D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase