Key result
The AGT-rs699-G allele was significantly associated with an increased risk of essential hypertension among Indian populations (OR 1.37).
Why the study?
Genetic association studies between candidate genes and hypertension yielded contradictory results across populations, and most meta-analyses failed to consider population genetic ancestry as a confounding factor.
Are specific genetic polymorphisms in AGT, CYP11B2, and ADRB2 associated with essential hypertension across different populations?
Meta-Analysis (n=23,120)
Are specific genetic polymorphisms in AGT, CYP11B2, and ADRB2 associated with essential hypertension across different populations?
Odds Ratio: 1.37 (95% CI 1.03–1.82)
p-value: p=0.03
Different genotype and allele frequencies in diverse populations result in distinct genetic associations with essential hypertension, highlighting the importance of considering genetic ancestry in pharmacogenetic approaches to hypertension management.
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.
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Maamor et al. (2024) conducted a meta-analysis in Essential hypertension (n=23,120). AGT-rs699, CYP11B2-rs1799998, and ADRB2-rs1042713/rs1042714 gene polymorphisms vs. Normotensive controls (non-carriers) was evaluated on Essential hypertension (AGT-rs699-G allele in Indian population) (OR 1.37, 95% CI 1.03-1.82, p=0.03). The AGT-rs699-G allele was significantly associated with an increased risk of essential hypertension among Indian populations (OR 1.37).
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