Chiu Ming-Huang, Chang Chia-Hsiu, Tantoh Disline Manli, Hsu Tsui-Wen, Hsiao Chih-Hsuan, Zhong Ji-Han, Liaw Yung-Po
Department of Pulmonology and Respiratory Care, Cathay General Hospital, Taipei City, Taiwan.
Cardiovascular Center, Cathay General Hospital, Taipei City, Taiwan.
Front Cardiovasc Med. 2023 Oct 2;10:1159764. doi: 10.3389/fcvm.2023.1159764. eCollection 2023.
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.
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).
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).
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.
高血压的病因发病机制是多因素的，包括遗传、表观遗传和环境因素。遗传和表观遗传变化对高血压的联合作用尚不清楚。我们评估了台湾成年人中rs1801133单核苷酸多态性（SNP）和启动子甲基化与高血压的独立及交互关联。
我们从台湾生物银行（TWB）检索了1238名个体的数据，包括启动子甲基化、rs1801133基因型（CC、CT和TT）、基本人口统计学、个人生活方式习惯和疾病史。
rs1801133基因型（CC、CT和TT）个体中高血压和启动子甲基化四分位数（β＜0.1338、0.1338≤β＜0.1385、0.1385≤β＜0.1423和β≥0.1423分别对应＜Q1、Q1-Q2、Q2-Q3和≥Q3）的分布有显著差异（P＜0.05）。与参考基因型（CC）相比，TT基因型个体患高血压的风险显著更高：比值比（OR）；95%置信区间（CI）=2.718；1.503-4.914。CT和TT基因型与高血压关联的趋势呈剂量依赖性（P=0.0041）。启动子甲基化（与≥Q3相比的较低四分位数）与高血压无显著关联。然而，其与rs1801133的相互作用显著（P=0.0323）。按rs1801133基因型分层后，与≥Q3相比，较低的启动子甲基化四分位数（＜Q1、Q1-Q2、Q2-Q3）与携带CC基因型个体患高血压的较高风险显著相关：Q2-Q3、Q1-Q2和＜Q1的OR（95%CI）分别为3.225（1.140-9.124）、4.177（1.424-12.247）和8.645（2.513-29.739）。趋势检验显著（P=0.0009）。
独立来看，rs1801133 TT与较高的高血压风险相关，但甲基化并非如此。基于基因型，较低的甲基化与CC基因型个体患高血压的较高风险呈剂量依赖性相关。我们的研究结果表明，rs1801133和启动子甲基化可能共同影响高血压易感性。
