Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis

Wu, Xiaoming; Yang, Kunxian; Tang, Xiaodan; Sa, Yalian; Zhou, Ruoyu; Liu, Jing; Luo, Ying; Tang, Wenru

doi:10.1007/s10815-014-0408-8

Cited by 50 publications

(44 citation statements)

References 83 publications

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“…A wide number of gene mutations were considered to be associated with the development of pre-eclampsia, but no single polymorphism was identified as having a clinically useful predictive performance (Table S4). The most frequently investigated genes were methylenetetrahydrofolate reductase (MTHFR) (n = 7) 25,26,38,48,91,102,140 and endothelial nitric oxide synthase (eNOS) (n = 7) 34,36,48,53,65,118,129 , and a number of genes relating to elements of the renin-angiotensinaldosterone system (RAAS) were investigated. The credibility of the association between the MTHFR C677T mutation and pre-eclampsia was generally weak and the association was not large.…”

Section: Genetic Markersmentioning

confidence: 99%

Prediction of pre‐eclampsia: review of reviews

Townsend

Khalil

Premakumar

et al. 2019

Ultrasound in Obstet & Gyne

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Objective Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre‐eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre‐eclampsia, to identify high‐value avenues for future research and to minimize future research waste in this field. Methods MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta‐analyses on the prediction of pre‐eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding. Results From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre‐eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre‐eclampsia, 31 (24.6%) investigated genetic associations with pre‐eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre‐eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta‐analysis. Thirty‐two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m2, with a specificity of 92% (95% CI, 89–95%) and a sensitivity of 21% (95% CI, 12–31%); BMI > 25 kg/m2, with a specificity of 73% (95% CI, 64–83%) and a sensitivity of 47% (95% CI, 33–61%); first‐trimester uterine artery pulsatility index or resistance index > 90th centile (specificity 93% (95% CI, 90–96%) and sensitivity 26% (95% CI, 23–31%)); placental growth factor (specificity 89% (95% CI, 89–89%) and sensitivity 65% (95% CI, 63–67%)); and placental protein 13 (specificity 88% (95% CI, 87–89%) and sensitivity 37% (95% CI, 33–41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation. Conclusions This review of reviews calls into question the need for further aggregate meta‐analy...

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Section: Genetic Markersmentioning

confidence: 99%

Prediction of pre‐eclampsia: review of reviews

Townsend

Khalil

Premakumar

et al. 2019

Ultrasound in Obstet & Gyne

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“…Another meta‐analysis regarding A1298C and RPL found no association . A meta‐analysis for PE published in 2015 found that C677T was a risk factor in Asian populations (OR = 1.47; 95% CI = 1.09‐1.98), but not in Caucasian and Latino populations in a dominant model, and this analysis found no increased risk for PE with A1298C . Jian Chen et al also found no connection between MTHFR C677T and PA .…”

Section: Discussionmentioning

confidence: 98%

“…Final overall meta-analysis of studies on MTHFR gene polymorphism and birth defects and adverse pregnancy outcome studies after stratification and/or sensitivity analyses in a dominant model, and this analysis found no increased risk for PE with A1298C 28. Jian Chen et al also found no connection between MTHFR C677T and PA 29.…”

mentioning

confidence: 94%

The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes

Zhang

Xiong

et al. 2018

Prenatal Diagnosis

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Published studies indicate the MTHFR C677T and A1298C polymorphisms are associated with abnormal homocysteine levels, which may cause various pregnancy complications and birth defects. However, the results obtained from different studies have been inconsistent. Therefore, this meta‐analysis explores the association between MTHFR polymorphisms and birth defects and adverse pregnancy outcomes. The PubMed, ScienceDirect, Embase, and China Biology Medicine literature databases and ClinicalTrials were searched. Analyses of public bias, meta‐regression, subgroups, and sensitivity were used to ensure the robustness of our results. MTHFR C677T was significantly associated with recurrent pregnancy loss in developing countries (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.20‐1.50) but not in developed countries (OR, 0.87; 95% CI, 0.68‐1.11). No significant relationship was found between MTHFR A1298C and recurrent pregnancy loss (OR, 1.04; 95% CI, 0.93‐1.18). MTHFR C677T and A1298C were not associated with preeclampsia (OR, 1.06; 95% CI, 0.97‐1.16 and OR, 1.16; 95% CI, 0.97‐1.39, respectively), and C677T was not associated with placental abruption (OR, 1.03; 95% CI, 0.87‐1.21), intrauterine growth retardation (OR, 1.02; 95% CI, 0.90‐1.15), or congenital heart disease (OR, 1.05; 95% CI, 0.89‐1.25). MTHFR C677T, but not A1298C, was associated with neural tube defects (OR, 1.24; 95% CI, 1.08‐1.42) and Down syndrome (OR, 1.65; 95% CI, 1.39‐1.95). Conclusion Although MTHFR C677T and A1298C are significantly associated with some types of congenital defects and adverse pregnancy outcomes, the impact of these polymorphisms is moderate.

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“…The preeclampsia is involved in many environmental factors, such as preexisting hypertension, diabetes and obesity as well as smoking (Wang et al, 2002;Chelbi et al, 2007). Moreover, many genetic factors also contribute to the development of this disease, such as interleukin (IL)-6, NLRP1 and MTHFR genes (Pontillo et al, 2015;Sowmya et al, 2015;Wu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Investigations into the association between polymorphisms in the interleukin-10 gene and risk of early-onset preeclampsia

Liu¹,

Fy²,

Xr³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. In this case-control study, we assessed the influence of IL-10 -1082A/G and -819T/C on the development of preeclampsia. The IL-10 -1082A/G and -819T/C polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism. The genotype distributions of the IL-10 -1082A/G and -819T/C polymorphisms in the control subjects were in conformance with Hardy-Weinberg equilibrium (HWE; P = 0.46 and 0.17). Unconditional logistic regression analyses revealed that individuals carrying the CC genotype of IL-10 -819T/C were associated with an increased risk of preeclampsia compared to the TT genotype. The odds ratio (95% confidence interval) for the CC genotype of IL-10

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Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis

Cited by 50 publications

References 83 publications

Prediction of pre‐eclampsia: review of reviews

Prediction of pre‐eclampsia: review of reviews

The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes

Investigations into the association between polymorphisms in the interleukin-10 gene and risk of early-onset preeclampsia

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