AGT, CYP11B2 & ADRB2 gene polymorphism & essential hypertension (HT): A meta-analysis

Abstract

Background & objectives The results of the genetic association studies between the selected candidate genes and hypertension (HT) contradicted across different populations. Majority of the meta-analyses carried out did not consider population genetic ancestry as a confounding factor. Therefore, this meta-analysis attempted to consolidate and re-evaluate the findings of the association between the selected candidate variants (AGT-rs699, CYP11B2-rs1799998, ADRB2-rs1042713 and rs1042714) and HT, by categorizing the genotyping data based on known genetic ancestry, and/or major geographical populations. Methods Publications were retrieved from PubMed, Cochrane and World of Science. The included articles were further divided into different populations based on their known genetic and/or geographical ancestry. Results AGTrs699-G was significantly associated with HT among Indians for (i) allele [P=0.03, Odds ratio (OR): 1.37, 95% Confidence Interval (CI): 1.03-1.82], and (ii) dominant mode of inheritance (P=0.009, OR:1.45, 95% CI: 1.09-1.91). CYP11B2rs1799998-G was significantly associated with HT in Europeans for (i) allele (P=6.9 × 10-5, OR: 0.82, 95% CI: 0.74-0.9), (ii) recessive (P=6.38 × 10-5, OR: 0.7, 95% CI: 0.59-0.83) and (iii) dominant mode of inheritance (P=0.008, OR: 0.81, 95% CI: 0.7-0.94). ADRB2-rs1042713-G was significantly associated with HT in east Asians for (i) allele (P=0.01, OR: 1.26, 95% CI: 1.05-1.51), and (ii) recessive mode of inheritance (P=0.04, OR: 1.36, 95% CI: 1.01-1.83). Interpretation & conclusions Different genotype and allele frequencies in diverse populations result in different genetic associations with HT across populations. This meta-analysis finding provides an update and summary of the genetic association between the selected simple nucleotide polymorphism (SNPs) and HT across different populations and essential insights into selecting appropriate pharmacogenetic marker(s) for effective HT management in populations of different ancestries.

Keywords: ADRB2-AGT; CYP11B2; essential hypertension; meta-analysis; populations.

Figure.

Summary of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow search process for AGT-rs699, CYP11B2 (rs1799998) and ADRB2 (rs1042713 and rs1042714). ESH, established hypertension; HT, hypertension; BP, blood pressure; NT, normotensive.