Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption.
OBJECTIVE
Heritable thrombophilias have been implicated as a potential cause of abruption by vascular disruption at the uteroplacental interface. Polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been linked to vascular complications outside of pregnancy, which includes stroke. Given the underlying thrombotic nature of abruption, we hypothesized that polymorphisms in the MTHFR gene are associated with abruption.


METHODS
We examined 2 variants in MTHFR: 677C-->T and 1298A-->C in genomic DNA extracted from maternal blood from the New Jersey-Placental Abruption Study, an ongoing, multicenter case-controlled study. We identified 195 women with a clinical diagnosis of abruption (cases) and 189 control subjects who were matched on race/ethnicity and parity. We assessed allele and genotype frequencies and their associations with abruption risk after adjusting for confounders through multivariable logistic regression analysis.


RESULTS
The wild-type allele (C) frequency of the 677C-->T variant of MTHFR among cases and control subjects was 69.0% and 64.3%, respectively; the wild-type allele (A) of the 1298A-->C variant was 75.9% and 79.4%, respectively. Distributions of the 677C-->T alleles among control subjects violated the Hardy-Weinberg equilibrium (P = .007); distributions of the 1298A-->C alleles were in equilibrium (P = .825). In comparison to the wild-type genotype (C/C), the homozygous mutant form (T/T) of 677C-->T was not associated with abruption (odds ratio, 0.60; 95% confidence interval [CI], 0.33-1.18). Similarly, the homozygous mutant form (C/C) of the 1298A-->C polymorphism was distributed equally between cases and control subjects (odds ratio, 2.28; 95% CI, 0.82-6.35). Plasma homocysteine and vitamin B12, but not folate, concentrations were elevated in cases compared with control subjects among women with the wild-type genotype of MTHFR 677C-->T (P = .039 for homocysteine; P = .048 for B12; P = .224 for folate).


CONCLUSIONS
In this population, neither heterozygosity nor homozygosity for the 677C-->T and 1298A-->C variants in MTHFR was associated with placental abruption.
Ananth
Cande V
CV
Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA. cande.ananth@umdnj.edu
Peltier
Morgan R
MR
De Marco
Celeste
C
Elsasser
Denise A
DA
Getahun
Darios
D
Rozen
Rima
R
Smulian
John C
JC
D000037:Abruptio Placentae / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D015810:Linkage Disequilibrium; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D012923:Social Class; D014805:Vitamin B 12 / Q000097:blood
D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12