Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 2:14:189-197.
doi: 10.2147/PGPM.S291277. eCollection 2021.

Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Peripheral Edema in Chinese Han Patients with Essential Hypertension

Hao Liang #  1   2 , Xinru Zhang #  3 , Zhuo Ma #  4 , Yan Sun  1   2 , Chang Shu  1 , Yihua Zhu  5   6 , Yanwei Zhang  6 , Songnian Hu  1   2 , Xiujuan Fu  3 , Lihong Liu  4
Affiliations

Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Peripheral Edema in Chinese Han Patients with Essential Hypertension

Hao Liang et al. Pharmgenomics Pers Med. .

Abstract

Background: Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5 (CYP3A4/5) in the liver. Peripheral edema emerges as the major adverse drug reaction to amlodipine and is the primary reason for discontinuation of amlodipine therapy. However, genetic changes in CYP3A5 may lead to changes in the tolerability of amlodipine.

Purpose: In this study, we were interested whether variants in CYP3A5 have a role to play in amlodipine-induced peripheral edema.

Methods: A total number of 240 Chinese Han patients that have experienced hypertension were included in the study. Sixty-four patients had experienced amlodipine-induced peripheral edema, while the remaining 176 patients with no history of edema formed the control group. Twenty-four single-nucleotide polymorphisms (SNPs) of CYP3A5 gene were sequenced by targeted region sequencing method. The relationship of these genetic variants with amlodipine-induced peripheral edema risk was assessed using logistic regression.

Results: The allele frequencies of CYP3A5*1D (rs15524), CYP3A5*1E (rs4646453) and CYP3A5*3 (rs776746) were significantly different between cases and controls (P<0.05). The CYP3A5 *3/*3 (CC) or CYP3A5 *1D/*1D (AA) carriers showed an increased risk of amlodipine-induced peripheral edema in dominant model. Meanwhile, patients carrying CYP3A5 *1E (AC/AA) showed a reduced risk of peripheral edema. Furthermore, we found a strong linkage disequilibrium among rs15524, rs4646453 and rs776746.

Conclusion: Our study reveals for the first time that CYP3A5 *1D, *1E and *3 were associated with amlodipine-induced peripheral edema in Chinese Han patients with hypertension. However, further studies comprising larger number of samples, more related genes and other factors are wanted.

Keywords: CYP3A5; SNP; amlodipine; edema; pharmacogenomics.

PubMed Disclaimer

Conflict of interest statement

All authors declare that they have no conflicts of interest for this work.

Figures

Figure 1
Figure 1
Linkage disequilibrium coefficients (|D’|) and LD block among the three polymorphisms of CYP3A5.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Flynn JT, Pasko DA. Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension. Pediatr Nephrol. 2000;15(3):302–316. doi:10.1007/s004670000480 - DOI - PubMed
    1. Sica DA. Pharmacotherapy review: calcium channel blockers. J Clin Hypertens (Greenwich). 2006;8(1):53–56. doi:10.1111/j.1524-6175.2005.04140.x - DOI - PMC - PubMed
    1. Fares H, DiNicolantonio JJ, O’Keefe JH, Lavie CJ. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes. Open Heart. 2016;3(2):e000473. doi:10.1136/openhrt-2016-000473 - DOI - PMC - PubMed
    1. Kala N, Babu S, Manjeu J, Aadivalavan A, Khan R. Allele-specific polymerase chain reaction for the detection of single nucleotide polymorphism in amlodipine-induced gingival enlargement. J Clin Pharm Ther. 2018;43(1):110–113. doi:10.1111/jcpt.12587 - DOI - PubMed
    1. Makani H, Bangalore S, Romero J, et al. Peripheral edema associated with calcium channel blockers: incidence and withdrawal rate–a meta-analysis of randomized trials. J Hypertens. 2011;29(7):1270–1280. doi:10.1097/HJH.0b013e3283472643 - DOI - PubMed

LinkOut - more resources