Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure.

Objective: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore...

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Publicado en:European Journal of Clinical Pharmacology Vol. 79; no. 5; pp. 663 - 671
Autores principales: Luo, Hong-Yu, Gao, Li-Chen, Long, Hui-Zhi, Zhou, Zi-Wei, Xu, Shuo-Guo, Li, Feng-Jiao, Li, Hong-Li, Cheng, Yan, Li, Cai-Xia, Peng, Xing-Yu, Li, Liang, Chen, Ran, Deng, Ping
Formato: research tables/charts Journal Article
Publicado: Springer Nature May2023
Acceso en línea:Ver este registro en EBSCOhost
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      dt: May2023
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-023-03484-6
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        atl: Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure.
      aug:
        au:
          Luo, Hong-Yu
          Gao, Li-Chen
          Long, Hui-Zhi
          Zhou, Zi-Wei
          Xu, Shuo-Guo
          Li, Feng-Jiao
          Li, Hong-Li
          Cheng, Yan
          Li, Cai-Xia
          Peng, Xing-Yu
          Li, Liang
          Chen, Ran
          Deng, Ping
        affil: School of Pharmacy, Department of Pharmacy, Phase I Clinical Trial Centre, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, 421001, Hengyang, China
      sug:
        subj:
          Polymorphism, Genetic
          Drug Efficacy
          Patient Safety
          Valsartan Therapeutic Use
          Chinese Persons
          Heart Failure
          Human
          Genotype
          Polymorphism, Single Nucleotide
          Logistic Regression
          Haplotypes
          Odds Ratio
          Confidence Intervals
          Hypotension
          Funding Source
      ab: Objective: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. Methods: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. Results: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287–8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012–0.723, P = 0.003; OR = 5.586, 95% CI: 1.621–19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. Conclusion: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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