Single Nucleotide Polymorphisms in Amlodipine-Associated Genes and Their Correlation with Blood Pressure Control among South African Adults with Hypertension

Charity Masilela; Oladele Vincent Adeniyi; Mongi Benjeddou

doi:10.3390/genes13081394

Single Nucleotide Polymorphisms in Amlodipine-Associated Genes and Their Correlation with Blood Pressure Control among South African Adults with Hypertension

Genes (Basel). 2022 Aug 5;13(8):1394. doi: 10.3390/genes13081394.

Authors

Charity Masilela¹, Oladele Vincent Adeniyi², Mongi Benjeddou³

Affiliations

¹ Department of Biochemistry, North West University, Mahikeng 2735, South Africa.
² Department of Family Medicine, Walter Sisulu University, East London 5200, South Africa.
³ Department of Biotechnology, Faculty of Natural Science, University of the Western Cape, Cape Town 7535, South Africa.

Abstract

Objective: This study describes the single nucleotide polymorphisms (SNPs) in amlodipine-associated genes and assesses their correlation with blood pressure control among South African adults with hypertension. Methods: In total, 304 hypertensive patients on amlodipine treatment belonging to the indigenous Swati, Xhosa and Zulu population groups of South Africa were recruited between June 2017 and June 2019. Participants were categorized into: controlled (blood pressure < 140/90 mmHg) and uncontrolled (blood pressure ≥ 140/90 mmHg) hypertension. Thirteen SNPs in amlodipine pharmacogenes with a high PharmGKB evidence base were selected and genotyped using MassArray (Agena BioscienceTM). Logistic regression was fitted to identify significant associations between the SNPs and blood pressure control with amlodipine. Results: The majority of the participants were females (76.6%), older than 45 years (89.1%) and had uncontrolled hypertension (52.3%). Of the 13 SNPs genotyped, five SNPs, rs1042713 (minor allele frequency = 45.9%), rs10494366 (minor allele frequency = 35.3%), rs2239050 (minor allele frequency = 28.7%), rs2246709 (minor allele frequency = 51.6%) and rs4291 (minor allele frequency = 34.4%), were detected among the Xhosa participants, while none were detected among the Swati and Zulu tribal groups. Variants rs1042713 and rs10494366 demonstrated an expression frequency of 97.5% and 79.5%, respectively. Variant TA genotype of rs4291 was significantly associated with uncontrolled hypertension. No association was established between blood pressure response to amlodipine and the remaining four SNPs. Conclusions: This study reports the discovery of five SNPs in amlodipine genes (rs2239050, rs2246709, rs4291, rs1042713 and rs10494366) among the indigenous Xhosa-speaking tribe of South Africa. In addition, the TA genotype of rs4291 was associated with blood pressure control in this cohort. These findings might open doors for more pharmacogenomic studies, which could inform innovations to personalised anti-hypertensive treatment in the ethnically diverse population of South Africa.

Keywords: South Africa; amlodipine; single nucleotide polymorphisms; uncontrolled hypertension.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amlodipine* / therapeutic use
Blood Pressure / genetics
Female
Humans
Hypertension* / drug therapy
Hypertension* / genetics
Male
Polymorphism, Single Nucleotide
South Africa

Substances

Amlodipine

Grants and funding

The work reported herein was made possible through funding by the South African Medical Research Council through its Division of Research Capacity Development under funding received from the South African National Treasury. Dr Charity Masilela was supported by the SAMRC Internship Program. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC.