Susceptibility to Hypertension Based on Rs1801133 Single Nucleotide Polymorphism and Promoter Methylation

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2023 Oct 18

PMID 37849939

Authors

Ming-Huang Chiu

Chia-Hsiu Chang

Disline Manli Tantoh

Tsui-Wen Hsu

Chih-Hsuan Hsiao

Ji-Han Zhong

Yung-Po Liaw

Affiliations

Soon will be listed here.

Abstract

Background: The aetio-pathologenesis of hypertension is multifactorial, encompassing genetic, epigenetic, and environmental factors. The combined effect of genetic and epigenetic changes on hypertension is not known. We evaluated the independent and interactive association of rs1801133 single nucleotide polymorphism (SNP) and promoter methylation with hypertension among Taiwanese adults.

Methods: We retrieved data including, promoter methylation, rs1801133 genotypes (CC, CT, and TT), basic demography, personal lifestyle habits, and disease history of 1,238 individuals from the Taiwan Biobank (TWB).

Results: The distributions of hypertension and promoter methylation quartiles (β < 0.1338, 0.1338 ≤ β < 0.1385, 0.1385 ≤ β < 0.1423, and β ≥ 0.1423 corresponding to <Q1, Q1-Q2, Q2-Q3, and ≥Q3) among individuals with the rs1801133 genotypes (CC, CT, and TT) were significantly different ( < 0.05). The risk of hypertension was significantly higher among individuals with the TT genotype compared to the reference genotype (CC): odds ratio (OR); 95% confidence interval (CI) = 2.718; 1.503-4.914. The trend of the association of the CT and TT genotypes with hypertension was dose-dependent ( = 0.0041). promoter methylation (lower quartiles compared to ≥Q3) was not significantly associated with hypertension. However, its interaction with rs1801133 was significant ( = 0.0323). After stratification by rs1801133 genotypes, lower promoter methylation quartiles (<Q1, Q1-Q2, Q2-Q3) compared to ≥Q3 were significantly associated with a higher risk of hypertension among individuals carrying the CC genotype: ORs (95% CIs) = 3.225 (1.140-9.124), 4.177 (1.424-12.247), and 8.645 (2.513-29.739) for Q2-Q3, Q1-Q2, and <Q1, respectively. The trend test was significant ( = 0.0009).

Conclusion: Independently, rs1801133 TT was associated with a higher risk of hypertension, but methylation was not. Based on genotypes, lower methylation was dose-dependently associated with a higher risk of hypertension in individuals with the CC genotype. Our findings suggest that rs1801133 and promoter methylation could jointly influence hypertension susceptibility.

Citing Articles

Association of Methylenetetrahydrofolate Reductase rs1801133 Polymorphism with osteoporosis and fracture risk in Taiwan.

Li M, Chen I, Yang H, Yen H, Ke Y, Chen Y Int J Med Sci. 2024; 21(12):2261-2271.

PMID: 39310265 PMC: 11413903. DOI: 10.7150/ijms.97524.

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