ArticlePloS one2011
Epistasis between COMT and MTHFR in maternal-fetal dyads increases risk for preeclampsia.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre-eclampsia risk: a meta-analysis.Molecular biology reports · 2014Pooled it
- Catechol-O-methyltransferase and Pregnancy Outcome: an Appraisal in Rat.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization.Frontiers in physiology · 2021Review
- Association Study of Single Nucleotide Polymorphisms of Endoplasmic Reticulum Aminopeptidase 1 and 2 Genes in Iranian Women with Preeclampsia.Iranian journal of public health · 2019Article
- Non-additive effects of ACVR2A in preeclampsia in a Philippine population.BMC pregnancy and childbirth · 2019Article
- Dopamine in the Pathophysiology of Preeclampsia and Gestational Hypertension: Monoamine Oxidase (MAO) and Catechol-O-methyl Transferase (COMT) as Possible Mechanisms.Oxidative medicine and cellular longevity · 2019Review
- Loss of placental growth factor ameliorates maternal hypertension and preeclampsia in mice.The Journal of clinical investigation · 2018Article
- Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations.Frontiers in physiology · 2018Review
- A Comparison of 2-Methoxyestradiol Value in Women with Severe Preeclampsia Versus Normotensive Pregnancy.Journal of clinical and diagnostic research : JCDR · 2017Article
- Protective Role of Maternal P.VAL158MET Catechol-O-Methyltransferase Polymorphism against Early-Onset Preeclampsia and its Complications.Journal of medical biochemistry · 2016Article
- 2-methoxyestradiol plasma levels are associated with clinical severity indices and biomarkers of preeclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2015Observational
- Detecting epistasis in human complex traits.Nature reviews. Genetics · 2014Review
- Malignant cancer and invasive placentation: A case for positive pleiotropy between endometrial and malignancy phenotypes.Evolution, medicine, and public health · 2014Review
- Polymorphisms in catechol-O-methyltransferase modify treatment effects of aspirin on risk of cardiovascular disease.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- The contribution of genetic and environmental factors to the duration of pregnancy.American journal of obstetrics and gynecology · 2014Review
- Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2013Review
- Fetal and maternal genes' influence on gestational age in a quantitative genetic analysis of 244,000 Swedish births.American journal of epidemiology · 2013Article
- A NovelMolecular genetics & genomic medicine · 2013Article
- Prolactin receptor gene polymorphisms are associated with gestational diabetes.Genetic testing and molecular biomarkers · 2013Article
- Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.Schizophrenia bulletin · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1α, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C → T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor "T" allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR.
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