Department of Pharmacy, University of Peshawar, Peshawar 25000, Pakistan.
District Headquarter Hospital (DHQH) Charsadda 24430, Pakistan.
Genes (Basel). 2023 May 29;14(6):1184. doi: 10.3390/genes14061184.
Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the Pakistani community prompted us to design this study. Aldosterone synthase () was thoroughly studied in different ethnic groups; however, no such study has been conducted in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. In essential hypertension, the aldosterone synthase gene () plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase () gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between gene polymorphism and hypertension in Pakistan's Pashtun population. We used the nascent exome sequencing method to identify variants associated with hypertension. The research was divided into two phases. In phase one, DNA samples from 200 adult hypertension patients (of age ≥ 30 years) and 200 controls were pooled (n = 200/pool) and subjected to Exome Sequencing. In the second phase, the WES reported SNPs were genotyped using the Mass ARRAY technique to verify and confirm the association between WES-identified SNPs and hypertension. WES identified a total of eight genetic variants in the gene. The chi-square test and logistic regression analysis were used to estimate the minor allele frequencies (MAFs) and chosen SNPs relationships with hypertension. The frequency of minor allele T was found to be higher in cases compared to the control (42% vs. 30%: = 0.001) for rs1799998 of gene, while no significant results ( > 0.05) were observed for the remaining SNPs; rs4536, rs4537, rs4545, rs4543, rs4539, rs4546 and rs6418 showed no positive association with HTN in the studied population (all > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan.
全基因组关联研究显著增加了高血压风险变异体的数量；然而，大多数研究都集中在欧洲社会。在发展中国家，包括巴基斯坦，缺乏这样的研究。由于缺乏研究和巴基斯坦社区高血压的高患病率，我们设计了这项研究。醛固酮合酶（）在不同种族群体中得到了深入研究；然而，在巴基斯坦开伯尔-普赫图赫瓦的普什图人中，尚未进行过此类研究。在原发性高血压中，醛固酮合酶基因（）起着重要作用。醛固酮的合成受遗传和环境因素的影响。醛固酮合酶（由基因编码）控制脱氧皮质酮向醛固酮的转化，因此具有遗传影响。基因中的多态性与高血压的风险增加有关。以前关于醛固酮合酶（）基因多态性及其与高血压关系的研究结果不一致。本研究调查了巴基斯坦普什图人基因多态性与高血压之间的关系。我们使用新兴的外显子组测序方法来鉴定与高血压相关的变异体。该研究分为两个阶段。在第一阶段，将 200 名成年高血压患者（年龄≥30 岁）和 200 名对照者的 DNA 样本混合（每组 200 人）进行外显子组测序。在第二阶段，使用 Mass ARRAY 技术对 WES 报告的 SNPs 进行基因分型，以验证和确认 WES 鉴定的 SNPs 与高血压之间的关联。外显子组测序共鉴定出基因中的 8 个遗传变异。卡方检验和逻辑回归分析用于估计次要等位基因频率（MAFs）和所选 SNP 与高血压的关系。rs1799998 基因的 T 等位基因频率在病例中高于对照组（42%比 30%：= 0.001），而其余 SNPs 没有显著结果（>0.05）；rs4536、rs4537、rs4545、rs4543、rs4539、rs4546 和 rs6418 在研究人群中与 HTN 无阳性关联（所有 >0.05）。我们的研究结果表明，rs1799998 增加了巴基斯坦开伯尔-普赫图赫瓦的普什图人群对 HTN 的易感性。
