Reduced folate carrier 80A-->G polymorphism, plasma folate, and risk of placental abruption.
Folate deficiency and maternal smoking are strong risk factors for placental abruption. We assessed whether the reduced folate carrier [NM_194255.1: c.80A-->G (i.e., p.His27Arg)] (RFC-1) polymorphism was associated with placental abruption, and evaluated if maternal smoking modified the association between plasma folate and abruption. Data were derived from the New Jersey-Placental Abruption Study--a multicenter, case-control study of placental abruption (2002-2007). Maternal DNA was assayed for the RFC-1 c.80A-->G polymorphism using a PCR-dependent diagnostic test. Maternal folate (nmol/l) was assessed from maternal plasma, collected immediately following delivery. Due to assay limitations, folate levels at > or =60 nmol/l were truncated at 60 nmol/l. Therefore, case-control differences in folate were assessed from censored log-normal regression models following adjustment for potential confounders. Distribution of the mutant allele (G) of the RFC-1 c.80A-->G polymorphism was similar between cases (52.3%; n = 196) and controls (50.5%; n = 191), as was the homozygous mutant (G/G) genotype (OR 1.1, 95% CI 0.6-2.2). In a sub-sample of 136 cases and 140 controls, maternal plasma folate levels (mean +/- standard error) corrected for assay detection limits were similar between placental abruption cases (63.6 +/- 5.1 nmol/l) and controls (58.3 +/- 4.7 nmol/l; P = 0.270), and maternal smoking did not modify this relationship (interaction P = 0.169). We did not detect any association between the RFC-1 c.80A-->G polymorphism and placental abruption, nor was an association between plasma folate and abruption risk evident. These findings may be the consequence of high prevalence of prenatal multivitamin and folate supplementation in this population (over 80%). It is therefore not surprising that folate deficiency may be rare and that the RFC-1 c.80A-->G polymorphism is less biologically significant for placental abruption.
Ananth
Cande V
CV
Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901-1977, USA. cande.ananth@umdnj.edu
Peltier
Morgan R
MR
Moore
Dirk F
DF
Kinzler
Wendy L
WL
Leclerc
Daniel
D
Rozen
Rima R
RR
D000037:Abruptio Placentae / Q000097:blood* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood*; D020022:Genetic Predisposition to Disease; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D058978:Reduced Folate Carrier Protein; D012306:Risk; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid