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Cited by 59Folate and B Vitamins ResearchPregnancy and preeclampsia studiesBlood Coagulation and Thrombosis Mechanisms

Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption

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Ananth, Cande V., Elsasser, Denise A., Kinzler, Wendy L., Peltier, Morgan R., Getahun, Darios, Leclerc, Daniel, Rozen, Rima R.·2007·Molecular Genetics and Metabolism
DOI 10.1016/j.ymgme.2007.02.004PMC PMC1885454
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Abstract

Objectives 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.Methods 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.Results 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.Conclusions In this population, there was an association between the homozygous mutant form of BHMT (742G-->A) polymorphism and increased risk for placental abruption.

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  • Iron deficiency anemia, infection and other inflammatory states, folate deficiency, and hyperhomocysteinemia are associated with increased risk of abruption.

    “Pregnant people with iron deficiency anemia, infection and other inflammatory states, as well as folate deficiency and hyperhomocysteinemia are also at increased risk (33–36).”

    From Placental abruption at near-term and term gestations: Pathophysiology, epidemiology, diagnosis, and management (2023) · cites this paper as [35]

    The introductory passage under Conclusions (page not provided) lists folate deficiency and intra-amniotic infections among risk factors for placental abruption. Our copy does not identify iron-deficiency anemia or inflammatory states generally as risk factors; it discusses elevated homocysteine as a possible contributor to abruption rather than establishing the claimed association. (LLM, conf=0.88)

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Authors
Ananth, C. V., Elsasser, D. A., Kinzler, W. L., Peltier, M. R., Getahun, D., Leclerc, D., & Rozen, R. R.
Affiliations
McGill University (CA)
Corresponding author
Ananth, Cande V.
ORCID
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2007-05
Volume
91
Issue
1
Pages
104-110
ISSN
1096-7192 (ISSN-L)
DOI
10.1016/j.ymgme.2007.02.004
PMC
PMC1885454
OpenAlex
W2066634394
Cited by
59
References
36
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2020: 1 · 2019: 3 · 2018: 5 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 6
FWCI
4.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Genetics and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD038902, R01HD038902)
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
placental abruption, methionine synthase reductase, MTRR, BHMT, genetic polymorphism, hyperhomocysteinemia, homocysteine metabolism, pregnancy complications, genetic susceptibility, maternal race
MeSH terms
Abruptio Placentae, Adolescent, Adult, Female, Ferredoxin-NADP Reductase, Folic Acid, Gene Frequency, Genotype, Homocysteine, Humans, Polymorphism, Genetic, Pregnancy, Risk Factors, Vitamin B 12, Case-Control Studies, Betaine-Homocysteine S-Methyltransferase

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