MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress

Rahimi, Zohreh; Malek-Khosravi, Shohreh; Rahimi, Ziba; Jalilvand, Faranak; Parsian, Abbas

doi:10.1016/j.clinbiochem.2012.10.020

Cited by 24 publications

(5 citation statements)

References 37 publications

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“…Reduced MTHFR enzyme activity can also alter genome instability with free radicals causing accumulation of toxins [ 14 ]. To date, numerous epidemiological studies and meta-analyses [ 9 , 20 , 21 , 22 ] confirmed that MTHFR C677T [ 10 , 17 , 23 , 24 ] and MTHFR A1298C [ 13 , 24 , 25 ] polymorphisms are associated with HDP; however, with inconsistent findings [ 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Meta-Prediction of MTHFR Gene Polymorphisms and Air Pollution on the Risk of Hypertensive Disorders in Pregnancy Worldwide

Yang

Shiao

2018

IJERPH

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Hypertensive disorders in pregnancy (HDP) are devastating health hazards for both women and children. Both methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and air pollution can affect health status and result in increased risk of HDP for women. The major objective of this study was to investigate the effect of MTHFR polymorphisms, air pollution, and their interaction on the risk of HDP by using meta-predictive analytics. We searched various databases comprehensively to access all available studies conducted for various ethnic populations from countries worldwide, from 1997 to 2017. Seventy-one studies with 8064 cases and 13,232 controls for MTHFR C677T and 11 studies with 1425 cases and 1859 controls for MTHFR A1298C were included. MTHFR C677T homozygous TT (risk ratio (RR) = 1.28, p < 0.0001) and CT plus TT (RR = 1.07, p = 0.0002) were the risk genotypes, while wild-type CC played a protective role (RR = 0.94, p = 0.0017) for HDP. The meta-predictive analysis found that the percentage of MTHFR C677T TT plus CT (p = 0.044) and CT (p = 0.043) genotypes in the HDP case group were significantly increased with elevated levels of air pollution worldwide. Additionally, in countries with higher air pollution levels, the pregnant women with wild-type CC MTHFR 677 had a protection effect against HDP (p = 0.014), whereas, the homozygous TT of MTHFR C677T polymorphism was a risk genotype for developing HDP. Air pollution level is an environmental factor interacting with increased MTHFR C677T polymorphisms, impacting the susceptibility of HDP for women.

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Section: Introductionmentioning

confidence: 99%

Meta-Prediction of MTHFR Gene Polymorphisms and Air Pollution on the Risk of Hypertensive Disorders in Pregnancy Worldwide

Yang

Shiao

2018

IJERPH

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“…Genetic studies of MTHFR in relation to development of preeclampsia, hypertensive gestational diseases, or CVD have mainly investigated genetic associations with the separate disorders, not focusing on possible pleiotropic effects on both conditions. The preeclampsia studies conducted to date have largely focused on a missense MTHFR SNP, rs1801133, and a regulatory MTHFR SNP, rs1801131 [38,59] and identified an association between the minor alleles and an increased risk of preeclampsia. The MTHFR SNP associated with preeclampsia in our HUNT cohort, rs17367504, is not in linkage disequilibrium with either of the two SNPs (rs1801133 and rs1801131, r 2 < 0.5).…”

Section: Discussionmentioning

confidence: 99%

The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia

Thomsen

McCarthy

Melton

et al. 2017

Journal of Hypertension

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Objective:Preeclampsia is a complex heterogeneous disease commonly defined by new-onset hypertension and proteinuria in pregnancy. Women experiencing preeclampsia have increased risk for cardiovascular diseases (CVD) later in life. Preeclampsia and CVD share risk factors and pathophysiologic mechanisms, including dysregulated inflammation and raised blood pressure. Despite commonalities, little is known about the contribution of shared genes (pleiotropy) to these diseases. This study aimed to investigate whether genetic risk factors for hypertension or inflammation are pleiotropic by also being associated with preeclampsia.Methods:We genotyped 122 single nucleotide polymorphisms (SNPs) in women with preeclampsia (n = 1006) and nonpreeclamptic controls (n = 816) from the Norwegian HUNT Study. SNPs were chosen on the basis of previously reported associations with either nongestational hypertension or inflammation in genome-wide association studies. The SNPs were tested for association with preeclampsia in a multiple logistic regression model.Results:The minor (G) allele of the intronic SNP rs17367504 in the gene methylenetetrahydrofolate reductase (MTHFR) was associated with a protective effect on preeclampsia (odds ratio 0.65, 95% confidence interval 0.53–0.80) in the Norwegian cohort. This association did not replicate in an Australian preeclampsia case–control cohort (P = 0.68, odds ratio 1.05, 95% confidence interval 0.83–1.32, minor allele frequency = 0.15).Conclusion:MTHFR is important for regulating transmethylation processes and is involved in regulation of folate metabolism. The G allele of rs17367504 has previously been shown to protect against nongestational hypertension. Our study suggests a novel association between this allele and reduced risk for preeclampsia. This is the first study associating the minor (G) allele of a SNP within the MTHFR gene with a protective effect on preeclampsia, and in doing so identifying a possible pleiotropic protective effect on preeclampsia and hypertension.

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“…Excessive release promotes thrombosis, reduces placental perfusion, and triggers the release of factors that culminates the clinical entity of PE [13]. Rahimi et al indicated that methylenetetrahydrofolate reductase C677T polymorphism through effects on triacylglycerol level, lipid peroxidation and oxidative stress might be involved in the pathogenesis of severe PE [14]. However, systematic review and meta-analysis performed by Zhao et al did not support AGTR1 +1166A>C as a susceptibility locus for PE, and they recommended other AGTR1 SNPs to be investigated.…”

Section: Genomicsmentioning

confidence: 99%

Preeclampsia at the molecular level

El-Desouki¹

2015

Appl Med Res

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In clinical practice, we found despite the promise of some biomarkers in identifying women at increased risk for preeclampsia (PE) is still challenging! PE is a pregnancy-specific syndrome causes substantial maternal and fetal/neonatal morbidity and mortality worldwide. Despite decades of research, the etiology is incompletely understood and hence the ability of clinicians to predict PE prior to the onset of symptoms has not improved significantly. In this review, we will explore potential future areas of research underlying the pathophysiology of PE at the molecular level and potential biomarkers evolving for early prediction and diagnosis hoping to suggest novel therapeutic interventions

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MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress

Cited by 24 publications

References 37 publications

Meta-Prediction of MTHFR Gene Polymorphisms and Air Pollution on the Risk of Hypertensive Disorders in Pregnancy Worldwide

Meta-Prediction of MTHFR Gene Polymorphisms and Air Pollution on the Risk of Hypertensive Disorders in Pregnancy Worldwide

The antihypertensive MTHFR gene polymorphism rs17367504-G is a possible novel protective locus for preeclampsia

Preeclampsia at the molecular level

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