Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

Issa, Mustafa Hassan; Cerda, Álvaro; Genvigir, Fabiana Dalla Vecchia; Cavalli, Selma Andrea; Bertolami, Marcelo Chiara; Faludi, André Árpád; Hirata, Mário Hiroyuki; Hirata, Rosário Dominguez Crespo

doi:10.1016/j.jsbmb.2011.11.001

Cited by 12 publications

(6 citation statements)

References 40 publications

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“…As reported by previous studies, we found an association of APOE *2 allele with lower risk for hypercholesterolemia (OR: 0.27, CI95%; 0.01-0.85, p=0.025) (Cerda et al, 2011b). Interestingly, APOE *3*3 genotype carriers had greater reduction of APOE mRNA levels in PBMC after atorvastatin treatment (Issa et al, 2012). Another study investigated the APOE g.4798T>G in subjects with statin-controlled dyslipidemia and did not find association with oxidative stress biomarkers and plasma tocopherol (Botelho et al, 2012).…”

Section: Lipid Metabolism-related Genessupporting

confidence: 84%

“…APOE alleles did not influence plasma lipids after long term treatment with simvastatin (Fiegenbaum et al, 2005b) and short term treatment with atorvastatin (Cerda et al, 2011b). We also reported no association between APOE genotypes and lipid-lowering response to atorvastatin combined or not with hormonal therapy for three months in postmenopausal HC women (Issa et al, 2012). As reported by previous studies, we found an association of APOE *2 allele with lower risk for hypercholesterolemia (OR: 0.27, CI95%; 0.01-0.85, p=0.025) (Cerda et al, 2011b).…”

Section: Lipid Metabolism-related Genesmentioning

confidence: 47%

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Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Hirata

Cerda

Genvigir

et al. 2018

Braz. J. Pharm. Sci.

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Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipidlowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.

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Section: Lipid Metabolism-related Genessupporting

confidence: 84%

Section: Lipid Metabolism-related Genesmentioning

confidence: 47%

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Hirata

Cerda

Genvigir

et al. 2018

Braz. J. Pharm. Sci.

Self Cite

View full text Add to dashboard Cite

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“…However, these side effects do not exceed the benefits promoted by the hypercholesterolemia therapy [ 14 , 15 ]. More importantly, even postmenopausal patients show a significant reduction of atherosclerosis after being treated with statins [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Relaxation Mechanisms and Oxidative Stress Are Restored by Atorvastatin Therapy in Ovariectomized Rats

et al. 2013

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The studies on hormone replacement therapy (HRT) in females with estrogen deficiency are not conclusive. Thus, non-estrogen therapies, such as atorvastatin (ATO), could be new strategies to substitute or complement HRT. This study evaluated the effects of ATO on mesenteric vascular bed (MVB) function from ovariectomized (OVX) female rats. Female rats were divided into control SHAM, OVX, and OVX treated with 17β-estradiol (EST) or ATO groups. The MVB reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine staining, and the expression of target proteins by western blot. The reduction in acetylcholine-induced relaxation in OVX rats was restored by ATO or EST treatment. The endothelium-dependent nitric oxide (NO) component was reduced in OVX rats, whereas the endothelium-derived hyperpolarizing factor (EDHF) component or prostanoids were not altered in the MVBs. Endothelial dysfunction in OVX rats was associated with oxidative stress, an up-regulation of iNOS and NADPH oxidase expression and a down-regulation of eNOS expression. Treatment with ATO or EST improved the NO component of the relaxation and normalized oxidative stress and the expression of those signaling pathways enzymes. Thus, the protective effect of ATO on endothelial dysfunction caused by estrogen deficiency highlights a significant therapeutic benefit for statins independent of its effects on cholesterol, thus providing evidence that non-estrogen therapy could be used for cardiovascular benefit in an estrogen-deficient state, such as menopause.

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“…Nevertheless, researchers have reported their attempts to combine genetic variants with different aspects of menopausal syndromes [ 3 , 5 , 6 , 32 ]. We selected two genes in our study: one for APOE and one for LEP , on the basis of biological conditions mentioned in [ 33 , 34 , 35 , 36 , 37 , 38 ] to be associated with menopause.…”

Section: Discussionmentioning

confidence: 99%

“…et al [ 36 ], in their study of APOE3 , suggest that obesity or metabolic syndrome risk should be effectively managed in APOE3 isoform groups to reduce serum LDL in postmenopausal Korean women. In a different study, Issa et al [ 37 ] found that menopause is associated with changes in lipid levels, resulting in an increased risk of atherosclerosis and cardiovascular events. They noticed that medication used to lower the level of cholesterol (Atorvastatin) downregulates the APOE mRNA expression and is modified by APOE genotypes in peripheral blood mononuclear cells from postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause

Rył

Jasiewicz

Grzywacz

et al. 2016

IJERPH

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Background: Menopause is the permanent cessation of menstruation due to loss of ovarian follicular activity. A review of the available literature indicates that correlations between the changes that take place in a woman’s body after menopause and different genetic variants are still being sought. Methods: The study was conducted in 252 women who had completed physiological menopause. The women were divided into groups according to the time elapsed since menopause. The total concentrations of estradiol and follicle-stimulating hormone were determined by means of electrochemiluminescence. The apolipoprotein E (APOE) and lepitn (LEP) genotypes were determined by real-time PCR and polymerase chain reaction–restriction fragment length polymorphism, respectively. Results: We observed that people with the APOE3/E3 genotype entered menopause insignificantly later compared to other genotypes. Additionally, in the group of patients with the APOE3/E3 genotypes, differences in the E2 concentration were significantly related to the time since their last menstruation. There is no association found in the literature between these polymorphisms of the LEP gene and hormones. Conclusions: To date, attempts to formulate a model describing the association between E2 and FSH concentration with the polymorphisms of various genes of menopause in women have not been successful. This relationship is difficult to study because of the number of nongenetic factors. Environmental factors can explain variation in postmenopausal changes in hormone levels.

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Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

Cited by 12 publications

References 40 publications

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Endothelial Relaxation Mechanisms and Oxidative Stress Are Restored by Atorvastatin Therapy in Ovariectomized Rats

Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause

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