Association of APP gene polymorphisms and promoter methylation with essential hypertension in Guizhou: a case–control study

Abstract

Abstract Background Single-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein (APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case–control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations. Objective and methods We conducted a case–control study on 343 EH patients and 335 healthy controls (including Miao, Buyi, and Han populations) in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms (rs2040273, rs63750921, rs2211772, rs2830077, rs467021, rs368196, rs466433, rs364048, rs364051, rs438031, rs463946) in the APP gene via MassARRAY SNP. The MassARRAY EpiTYPER was employed to detect the methylation levels of the promoters. Results In the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (χ 2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype (OR 0.105, 95%CI 0.012–0.914, P = 0.041). For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype (OR 0.533, 95%CI 0.294–0.965, P = 0.038). Haplotype TCC (rs364051–rs438031–rs463946) increased the risk of EH in Guizhou (OR 1.427, 95%CI 1.020–1.996, P = 0.037). Each 1% increase in CpG_19 (− 613 bp) methylation level was associated with a 4.1% increase in hypertension risk (OR 1.041, 95%CI 1.002–1.081, P = 0.039). Each 1% increase in CpG_1 (− 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women (OR 0.920, 95%CI 0.860–0.984, P = 0.015). CpG_19 significantly correlated with systolic blood pressure (r = 0.2, P = 0.03). The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH (χ 2 = 7.633, P = 0.006). CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH (χ 2 = 19.874, P < 0.001). Conclusion In summary, rs2211772 polymorphism and promoter methylation level of APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.

Keywords

• Essential hypertension
• Amyloid precursor protein
• Gene polymorphism
• Promoter methylation
• Guizhou minorities