Differences in 4-hydroxyestradiol levels in leukocytes are related to CYP1A1∗2C, CYP1B1∗3 and COMT Val158Met allelic variants

Martínez-Ramírez, Ollin Celeste; Pérez‐Morales, Rebeca; Petrosyan, Pavel; Castro-Hernández, Clementina; Gonsebatt, María E.; Rubio, Julieta

doi:10.1016/j.steroids.2015.06.014

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…Namely, catechins and their metabolites, which belong to one of the main aronia polyphenol classes-proanthocyanidins (32), can increase the production of S-adenosyl-L-homocysteine (SAH), a potent inhibitor of DNMTs and a participant of the folate-methionine cycle, through the inhibition of catechol-Omethyltransferase (COMT)-mediated O-methylation of catechol substrates (33,34). Among the main endogenous substrates for both liver and leukocyte, COMT is a catechol estrogen (33,35), potentially explaining the finding of the present methylation analysis exclusively in women. In addition, catechins suppress MTHFR activity, hence blocking the folate-methionine cycle and reducing the methyl group bioavailability (36).…”

Section: Discussionmentioning

confidence: 99%

Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women

et al. 2021

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Cardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD.

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Section: Discussionmentioning

confidence: 99%

Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women

et al. 2021

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“…A number of studies have indicated that the level of cell sensitivity to the influence of 4OHE2 is determined by polymorphisms of genes whose products are involved in the metabolism of steroid hormones [22][23][24]. These include cytochromes CYP 1A1 and CYP 1B1, which catalyze the conversion of estrogens to catechol estrogens, as well as catechol-o-methyltransferase (COMT) and glutathione-S-transferase 1 (GSTP1), responsible for the final stages of inactivation of estrogen.…”

Section: Discussionmentioning

confidence: 99%

“…These include cytochromes CYP 1A1 and CYP 1B1, which catalyze the conversion of estrogens to catechol estrogens, as well as catechol-o-methyltransferase (COMT) and glutathione-S-transferase 1 (GSTP1), responsible for the final stages of inactivation of estrogen. It was shown that the polymorphic variants of the genes CYP 1A1*2C, CYP 1B1*3, COMT Val158Met and GSTP1 Ile105Val are associated with an increased amount of the 4OHE2 in leukocytes compared to cells carrying wild-type alleles [22]. Along with this, the presence of the CYP 1B1*3 Leu432Val isoform is associated with the risk of developing several types of cancer, including EC [23].…”

Section: Discussionmentioning

confidence: 99%

Sensitivity to 4-Hydroxyestradiol and Dna Repair Efficiency in Peripheral Blood Lymphocytes of Endometrial Cancer Patients

Buchynska¹,

Brieieva²

2018

Exp. Onc.

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Background: The development of hormone-dependent cancers, including endometrial carcinomas, in great part may be mediated by the genotoxic effects of estrogen metabolites, among which 4-hydroxyestradiol (4OHE2) is characterized by the most prominent DNA-damaging properties. It is assumed that the individual sensitivity to the 4OHE2 may determine the predisposition to endometrial cancer (EС). Aim: To analyze the sensitivity of peripheral blood lymphocytes (PBLs) of EC patients to the 4OHE2 and to evaluate the repair efficiency of 4OHE2-induced DNA damage. Materials and Methods: The study was performed on the PBLs of 53 EC patients and 20 healthy women. The level of DNA damage was measured using the comet assay and was expressed as % tail DNA. The DNA repair efficiency (%) was evaluated by determining the ratio between the amount of repaired DNA damage and the level of 4OHE2-induced damage that appeared after incubation of PBLs with 4OHE2. Results: In PBLs of EC patients, a higher level of 4OHE2-induced DNA damage (32.0 ± 2.2% tail DNA) and lower DNA repair efficiency (34.0 ± 4.5%) was observed compared to PBLs of healthy women (22.3 ± 2.3% tail DNA and 48.8 ± 4.5%, respectively). PBLs of EC patients with deep tumor invasion of myometrium were characterized by more prominent decrease of DNA repair than those with less invasive tumor (< ½ of myometrium) (20.9 ± 7.8 and 43.7 ± 6.7%, respectively). Furthermore, lower DNA repair efficiency was detected in the PBLs of EC patients with a family history of cancer compared to this parameter in patients with sporadic tumors (20.9±7.8 and 47.1 ± 5.5%, respectively). Conclusion: The PBLs of EC patients are characterized by increased sensitivity to the genotoxic effect of 4OHE2 and reduced repair efficiency regarding 4OHE2-induced DNA damage. A lower level of DNA repair is observed in EC patients with deep tumor myometrial invasion and a family history of cancer.

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Sex hormones and genetic variants in hormone metabolic pathways associated with the risk of colorectal cancer

Chen

Xie

et al. 2020

Environment International

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Differences in 4-hydroxyestradiol levels in leukocytes are related to CYP1A1∗2C, CYP1B1∗3 and COMT Val158Met allelic variants

Cited by 4 publications

References 41 publications

Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women

Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women

Sensitivity to 4-Hydroxyestradiol and Dna Repair Efficiency in Peripheral Blood Lymphocytes of Endometrial Cancer Patients

Sex hormones and genetic variants in hormone metabolic pathways associated with the risk of colorectal cancer

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