NOS3 rs3918188C>A is associated with susceptibility to resistant hypertension while CES1 genetic variation was not associated with resistant hypertension among South Africans.

IF 2.8 3区生物学 Q2 GENETICS & HEREDITY

Frontiers in Genetics Pub Date : 2025-06-04 eCollection Date: 2025-01-01 DOI:10.3389/fgene.2025.1608423

Jonathan N Katsukunya, Revina Naicker, Nyarai D Soko, Dirk Blom, Phumla Sinxadi, Emile R Chimusa, Brian Rayner, Erika Jones, Collet Dandara

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引用次数: 0

Abstract

Introduction: Genetic variation in genes coding for enzymes metabolising antihypertensive drugs, may affect the efficacy of angiotensin converting enzyme (ACE) inhibitors such as enalapril, potentially leading to resistant hypertension (RHTN). We set out to evaluate the contribution of genetic variation in CES1 and NOS3 genes on susceptibility to RHTN, as well as estimate the frequencies of CES1 copy number variation (CNV) in African and Mixed Ancestry (MA) populations of South Africa.

Methods: Using a retrospective age, sex and ethnicity matched case-control study design, 379 participants with hypertension belonging to the African and MA ethnic groups were recruited. Cases were participants with RHTN (i.e., blood pressure (BP) ≥140/90 mmHg on ≥3 antihypertensive drugs or BP < 140/90 mmHg on >3 antihypertensive drugs, including a diuretic). Cases were matched to controls with similar characteristics (age (±5 years), sex and ethnicity) in a 1:1 ratio. Controls were participants with hypertension that was under control (BP < 140/90 mmHg on ≤3 antihypertensive drugs). Five polymorphisms in CES1 and NOS3 were characterized using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), quantitative PCR and validated using Sanger sequencing. The additive model of inheritance and multivariable logistic regression were used to determine associations between genotypes and RHTN while adjusting for potential confounding variables.

Results and discussion: NOS3 rs3918188A/A (aOR: 0.13; CI: 0.04-0.41; P = 0.0009) genotype and NOS3 rs2070744-rs1798883-rs3918188G-T-A haplotype (OR: 0.54; CI: 0.37-0.78; P = 0.001) appeared to confer protection against RHTN among MA participants only. CES1 rs2244613C>A and CES1 CNV were not significantly associated with RHTN. However, there appeared to be quantitative differences in CES1 CNV profiles across ethnic groups. We speculate that NOS3 rs3918188A allele may affect NOS3 gene expression, potentially leading to increased amounts of the vasodilator, nitric oxide (NO) and favourable outcomes in individuals taking antihypertensives drugs such as enalapril.

Conclusion: NOS3 genetic variation seems important in the susceptibility to RHTN among Africans and requires further studies.

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NOS3 rs3918188C>A与南非人对顽固性高血压的易感性相关，而CES1遗传变异与顽固性高血压无关。

导语：降压药代谢酶基因的遗传变异可能影响血管紧张素转换酶（ACE）抑制剂（如依那普利）的疗效，可能导致顽固性高血压（RHTN）。我们开始评估CES1和NOS3基因的遗传变异对RHTN易感性的贡献，并估计南非非洲和混合血统（MA）人群中CES1拷贝数变异（CNV）的频率。方法：采用回顾性年龄、性别和种族匹配的病例对照研究设计，招募了379名来自非洲和MA族群的高血压患者。病例为RHTN患者（即使用≥3种降压药时血压(BP)≥140/90 mmHg或使用包括利尿剂在内的bbb3降压药时血压< 140/90 mmHg）。病例与具有相似特征（年龄（±5岁）、性别和种族）的对照组按1:1的比例配对。对照组是高血压得到控制的参与者（服用≤3种降压药时血压< 140/90 mmHg）。采用聚合酶链反应-限制性片段长度多态性（PCR- rflp）、定量PCR对CES1和NOS3的5个多态性进行了表征，并采用Sanger测序进行了验证。采用遗传加性模型和多变量逻辑回归来确定基因型与RHTN之间的关系，同时调整潜在的混杂变量。结果与讨论：NOS3 rs3918188A/A (aOR: 0.13；置信区间:0.04—-0.41;P = 0.0009)基因型和NOS3 rs2070744-rs1798883-rs3918188G-T-A单倍型(OR: 0.54；置信区间:0.37—-0.78;P = 0.001)似乎仅在MA参与者中具有抗RHTN的保护作用。CES1 rs2244613C>A和CES1 CNV与RHTN无显著相关性。然而，CES1 CNV谱在不同种族之间似乎存在数量差异。我们推测，NOS3 rs3918188A等位基因可能影响NOS3基因的表达，可能导致血管扩张剂、一氧化氮（NO）的量增加，并在服用依那普利等降压药的个体中产生有利的结果。结论：NOS3基因变异在非洲人RHTN易感性中起重要作用，有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

5.50

自引率

8.10%

发文量

3491

审稿时长

14 weeks

期刊介绍： Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.