Hypomethylation of the Toll-like receptor-2 gene increases the risk of essential hypertension.

Abstract

Studies on the etiology of essential hypertension (EH) have demonstrated that chronic inflammation contributes to the onset and development of elevated blood pressure. Toll‑like receptors (TLRs), important immune receptors, serve a role in chronic inflammation and are associated with EH. In the present study, 96patients with EH, and 96 age‑ and sex‑matched healthy controls were recruited, and eight cytosine‑phosphate‑guanine (CpG) dinucleotides (CpG1‑8) were analyzed using bisulfite pyrosequencing technology. It was observed that the methylation levels of all of the eight CpG dinucleotides were decreased in the EH group compared with the control group; however, only CpG1 (2.83±1.34 vs. 3.44±1.75; P=0.009), CpG6 (3.58±3.64 vs. 8.30±4.13; P<0.001) and CpG8 (8.91±5.32 vs. 11.33±3.87; P<0.001) were significantly different, as demonstrated by paired t‑test analysis. In addition, logistic regression analysis demonstrated that CpG6 hypomethylation was a risk factor of EH (odds ratio=1.10; adjusted P=0.009), and CpG6 methylation level was observed to be negatively correlated with systolic blood pressure (r=‑0.304; P<0.001) and diastolic blood pressure (r=‑0.329; P<0.001). Additionally, receiver operating characteristic curve analysis demonstrated that a methylation level of 7.5% for CpG6 (area under the curve, 0.834; P<0.001) was an appropriate threshold value to predict the risk of EH. With generalized multifactor dimensionality reduction, a potential gene‑gene interaction between CpG6 and CpG8 (P=0.001), and gene‑environment interactions between smoking, alcohol consumption, CpG6, CpG7 and CpG8 (P=0.011), were observed. In conclusion, the results of the present study demonstrated that hypomethylation of the TLR2 promoter, particularly CpG6, was associated with the risk of EH in this population. Additionally, a gene‑gene interaction between CpG6 and CpG8, and interactions between environmental factors, including smoking and alcohol consumption, and CpG6, CpG7 and CpG8, may be associated with the risk of EH.