The association between Alu hypomethylation and the severity of hypertension

Abstract

Introduction Epigenetic changes that cause genomic instability may be the basis of pathogenic processes of age-associated noncommunicable diseases (NCDs). Essential hypertension is one of the most common NCDs. Alu hypomethylation is an epigenetic event that is commonly found in elderly individuals. Epigenomic alterations are also found in age-associated NCDs such as osteoporosis and diabetes mellitus. Alu methylation prevents DNA from being damaged. Therefore, Alu hypomethylated DNA accumulates DNA damage and, as a result, causes organ function deterioration. Here, we report that Alu hypomethylation is a biomarker for essential hypertension. Results We investigated Alu methylation levels in white blood cells from normal controls, patients with prehypertension, and patients with hypertension. The hypertension group possessed the lowest Alu methylation level when classified by systolic blood pressure and diastolic blood pressure (P = 0.0002 and P = 0.0088, respectively). In the hypertension group, a higher diastolic blood pressure and a lower Alu methylation level were observed (r = -0.6278). Moreover, we found that changes in Alu hypomethylation in the four years of follow-up in the same person were directly correlated with increased diastolic blood pressure. Conclusions Similar to other age-associated NCDs, Alu hypomethylation is found in essential hypertension and is directly correlated with severity, particularly with diastolic blood pressure. Therefore, Alu hypomethylation may be linked with the molecular pathogenesis of high blood pressure and can be used for monitoring the clinical outcome of this disease.

Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels

“…Furthermore, the results demonstrated a direct correlation between Alu hypomethylation levels and high blood glucose in type 2 DM 50 . Moreover, this association is similar to the correlation between Alu hypomethylation and lower bone mass or hypertension patients 27,51 . Therefore, the aim of this study was to determine the correlation between changes in Alu methylation levels in individual patients, particularly those who had increased HbA1c levels, and the progression of type 2 DM.…”

“…50 Moreover, this association is similar to the correlation between Alu hypomethylation and lower bone mass or hypertension patients. 27,51 Therefore, the aim of this study was to determine the correlation between changes in Alu methylation levels in individual patients, particularly those who had increased HbA1c levels, and the progression of type 2 DM. Interestingly, our results revealed that Alu methylation levels were consistently reduced in the same individuals, with significantly decreased levels observed in the normal, pre-DM, and type 2 DM groups during the follow-up.…”

“…Type 2 DM is a multifactorial condition characterized by high blood glucose levels (hyperglycemia), 13–15 which are influenced by genetic and epigenetic factors 16–19 . DNA methylation, an epigenetic event commonly found in elderly individuals, exhibits changes in type 2 DM patients and correlates with poor health status in humans 20–27 …”

“…[16][17][18][19] DNA methylation, an epigenetic event commonly found in elderly individuals, exhibits changes in type 2 DM patients and correlates with poor health status in humans. [20][21][22][23][24][25][26][27] DNA methylation serves two fundamental purposes: genomic stability prevention and gene expression regulation. 28,29 Alu methylation, a specific form of DNA methylation, has been shown to play a role in minimizing the accumulation of endogenous DNA damage.…”

Genome wide hypomethylation and youth-associated DNA gap reduction promoting DNA damage and senescence-associated pathogenesis

“…The DNA hypomethylation of IRSs, particularly Alu elements and human endogenous retrovirus K and long interspersed nucleotide element-1 (LINE-1) to a lesser degree, is a common epigenomic alteration in elderly individuals(28-31). Alu hypomethylation has also been demonstrated in patients with age-associated NCDs, including diabetes, osteoporosis and essential hypertension (32)(33)(34). Interestingly, in newborns, Alu methylation is directly associated with the growth rate (35).…”