Association of Mineralocorticoid Receptor Polymorphism I180V With Left Ventricular Hypertrophy in Resistant Hypertension

Ritter, Alessandra Mileni Versuti; Fontana, Vanessa; Faria, Ana Paula; Modolo, Rodrigo; Barbaro, Natália R.; Sabbatini, A.; Peres, Heverton Alves; Biagi, Celso; Silva, Pamela S.; Lopes, Paulo César; Tanus‐Santos, José Eduardo; Coelho, Eduardo Barbosa; Moreno, Heitor

doi:10.1093/ajh/hpv070

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…Interestingly, in RHP, increased levels of aldosterone and more prevalent left ventricular hypertrophy were associated with Val180Ile polymorphism. 180Val/c.-2G haplotype also was associated with higher plasma aldosterone in RHP (Ritter et al, 2016).…”

Section: Pharmacodynamics-related Genesmentioning

confidence: 83%

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: Pharmacodynamics-related Genesmentioning

confidence: 83%

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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“…The results of this study show that the site polymorphism is associated with the risk of GH. Ritter et al [23] demonstrated the association of the rs5522 SNP with the resistant hypertension, while the rs2070951 locus c.-2C>G mutation was not associated. A study of serum aldosterone levels found a statistically significant difference in the levels between different genotypes of the rs5522 locus, but not between different genotypes of the rs2070951 locus.…”

Section: Discussionmentioning

confidence: 99%

NR3C2 gene polymorphism is associated with risk of gestational hypertension in Han Chinese women

Cui

Jiang

2019

Medicine

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Background: The influence of genetic polymorphisms on the development of gestational hypertension (GH) is unclear. The aim of this study was to examine whether single-nucleotide polymorphisms (SNPs) of the nuclear receptor subfamily 3, group C, member 2 (NR3C2) genes, rs5522, rs2070951, rs5534, s2248038, and s9992256 are associated with GH in Han Chinese women.Method: Sanger sequencing was used to analyze the genotypes of rs5522, rs2070951, rs5534, rs2248038, and rs9992256 loci of the NR3C2 gene in 450 patients with GH and 450 healthy controls.Results: The rs5522 dominant model (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.13-1.47, P < .001) and the recessive model (OR = 1.64, 95% CI: 1.33-1.86, P < .001) had higher GH risk. The rs2070951 dominant model (OR = 1.18, 95% CI: 1.03-1.35, P = .02) had higher risk of GH, and the recessive model (OR = 1.09, 95% CI: 0.84-1.34, P = .55) was not significant for GH risk. The rs5534 dominant model (OR = 1.25, 95% CI: 1.09-1.43, P = .001) had a higher GH risk. The rs2248038 and rs9992256 sites were not significantly related to GH risk. Gene-gene interactions at the rs5522, rs2070951, and rs5534 loci affected GH risk (OR = 1.34, 95% CI: 1.12-1.64, P < .001). Conclusion:The SNPs of the NR3C2 gene rs5522, rs2070951, and rs5534 are associated with GH in Han Chinese women.Abbreviations: BMI = body mass index, cCSC = chronic central serous chorioretinopathy, CI = confidence interval, DBP = diastolic blood pressure, GH = gestational hypertension, HR = heart rate, MDR = multifactor dimensionality reduction, MR = mineralocorticoid receptor, NR3C2 = the nuclear receptor subfamily 3, group C, member 2, OR = odds ratio, SBP = systolic blood pressure, SNP = single-nucleotide polymorphism.

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“…Genetic variation in the MR gene (Ile180Val) as well as its linked variants such as G215C and Ala241Val was reported to show reduced activity of MR in an in vitro assay (15), although the association with serum aldosterone level is controversial (16, 17). In this study, men carrying a homozygous variant with reduced activity of MR showed a worse prognosis when treated with ADT, which is consistent with the pre-clinical finding that decreased MR signaling was associated with increased cellular resistance to hormonal therapy (6).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of Genetic Polymorphism in Mineralocorticoid Receptor and Comorbidity With Hypertension in Androgen-Deprivation Therapy

et al. 2018

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Mineralocorticoid receptor (MR) signaling which is closely associated with hypertension plays important roles in resistance to antiandrogen therapy in prostate cancer. However, its impact on the prognosis in androgen-deprivation therapy (ADT) has not been elucidated. Then, we investigated the impact of genetic variation in MR and comorbidity with hypertension on the prognosis in ADT. This study included 182 Japanese patients with prostate cancer treated with ADT, whose comorbidity status with hypertension were available. The associations of MR polymorphism (rs5522) and comorbidity with hypertension with clinicopathological parameters as well as progression-free survival and overall survival were examined. Clinicopathological characteristics were comparable between genetic variation in MR. However, homozygous variant in MR was associated with shorter time to castration resistance (P = 0.014) and any-cause death (P = 0.024). In patients' background, presence of comorbidity with hypertension showed the trend with lower PSA level at diagnosis and lower biopsy Gleason score, as well as significant association with less incidence of N1. Comorbidity with hypertension was associated with longer time to castration resistance (P = 0.043) and any-cause death (P = 0.046), which was diminished on multivariate analysis including age, PSA level at diagnosis, biopsy Gleason score, clinical stage, and the modality of hormonal therapy. Genetic variation in MR (rs5522) and comorbidity with hypertension were significantly and potentially associated with prognosis when treated with ADT, respectively. This suggests that the individual intensity of MR signaling may be associated with resistance to ADT and a promising biomarker in ADT.

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Association of Mineralocorticoid Receptor Polymorphism I180V With Left Ventricular Hypertrophy in Resistant Hypertension

Abstract: Our study suggests that rs5522 polymorphism might affect cardiac remodeling and aldosterone levels in RHTN subjects.

Cited by 13 publications

References 36 publications

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

NR3C2 gene polymorphism is associated with risk of gestational hypertension in Han Chinese women

Prognostic Impact of Genetic Polymorphism in Mineralocorticoid Receptor and Comorbidity With Hypertension in Androgen-Deprivation Therapy

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