Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan

Abstract

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 (CYP11B2) 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 (CYP11B2) plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the CYP11B2 gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase (CYP11B2) gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between CYP11B2 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 CYP11B2 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%: p = 0.001) for rs1799998 of CYP11B2 gene, while no significant results (p > 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 p > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan.

Genetic Factors Contributing to the Pathogenesis of Essential Hypertension in Two African Populations

“…Delving into individual variants, the CYP11B2 rs1799998 variant, located in the promoter region of the CYP11B2 gene, exhibited associations with EH, thus corroborating studies linking this variant to higher plasma aldosterone-to-renin ratios and increased BP [ 60 , 61 ]. As an added layer to the complexity to the genetic landscape of EH, the prevalence of the C allele of the CYP11B2 rs1799998 variant has demonstrated ethnic variation globally [ 30 , 62 , 63 , 64 ].…”

Diuretic effects of Hecogenin and Hecogenin acetate via aldosterone synthase inhibition

“…CYP 11B2 encodes for aldosterone synthase, the enzyme responsible for the final steps in aldosterone biosynthesis. Upregulation of CYP 11B2 increases aldosterone production, potentially resulting in hypertension and electrolyte imbalance ( Shah et al, 2023 ). HEC and HA administered at doses of 5, 10, and 25 mg/kg) exhibited a significant and dose dependent reduction in CYP 11B2 gene expression in contrast to the control group (p < 0.001).…”

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

“…Hence, regular blood pressure monitoring is crucial for early detection and management (Hasanzadeh et al 2023). According to two empirical studies in Pakistan, which are based on National Health Survey and rural northern areas of the country, hypertension prevalence rate is 46.2% and 33%, respectively (Almas et al 2023;Shah et al 2023). If this number continues to increase then one out of every third person will be a victim of hypertension (Elahi et al 2023).…”