vitamin-b-12 and Abruptio-Placentae

Methionine synthase reductase (MTRR) and betaine-homocysteine S-methyltransferase (BHMT) are two enzymes that regulate homocysteine metabolism. Elevated homocysteine (hyperhomocysteinemia) is associated with adverse pregnancy outcomes and vascular disease. We assessed whether polymorphisms in MTRR (66A-->G; I22M) and BHMT (742G-->A; R239Q) were associated with abruption. We further evaluated whether homocysteine levels differed between cases and controls for MTRR and BHMT genotypes.. Data were derived from the New Jersey Placental Abruption Study (NJ-PAS)-an ongoing, multicenter, case-control study since August 2002. Women with a clinical diagnosis of abruption were recruited as incident cases (n=196), and controls (n=191) were matched to cases based on maternal race/ethnicity and parity. Total plasma homocysteine concentrations were evaluated in a subset of 136 cases and 136 controls. DNA was genotyped for the MTRR and BHMT polymorphisms.. Frequencies of the minor allele of MTRR were 40.8% and 42.2% in cases and controls, respectively (adjusted OR 0.79, 95% CI 0.45, 1.40). The corresponding rates for BHMT were 33.9% and 31.7%, respectively (adjusted OR 1.93, 95% CI 0.99, 4.09). Distributions for the homozygous mutant form of MTRR were similar between cases and controls (OR 1.18, 95% CI 0.62, 2.24). The rate of homozygous mutant BHMT genotype was 2.8-fold (OR 2.82, 95% CI 1.84, 4.97) higher in cases than controls. Stratification of analyses based on maternal race did not reveal any patterns in association.. In this population, there was an association between the homozygous mutant form of BHMT (742G-->A) polymorphism and increased risk for placental abruption.

Topics: Abruptio Placentae; Adolescent; Adult; Betaine-Homocysteine S-Methyltransferase; Case-Control Studies; Female; Ferredoxin-NADP Reductase; Folic Acid; Gene Frequency; Genotype; Homocysteine; Humans; Polymorphism, Genetic; Pregnancy; Risk Factors; Vitamin B 12

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.. 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.. 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).. In this population, neither heterozygosity nor homozygosity for the 677C-->T and 1298A-->C variants in MTHFR was associated with placental abruption.

Topics: Abruptio Placentae; Adolescent; Adult; Alleles; Case-Control Studies; DNA; Female; Folic Acid; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Linkage Disequilibrium; Methylenetetrahydrofolate Reductase (NADPH2); Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Pregnancy; Social Class; Vitamin B 12

Topics: Abruptio Placentae; Adult; Anemia, Macrocytic; Biological Assay; Bone Marrow Examination; Erythrocyte Count; Erythrocytes, Abnormal; Euglena; Female; FIGLU Test; Folic Acid Deficiency; Humans; Lactobacillus; Leukocyte Count; Maternal Mortality; Methods; Neutrophils; Pregnancy; Vitamin B 12