The goal of our study is to investigate the contribution of promoter DNA methylation of α-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = −0.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (>50 years) women than pre-menopausal (≤50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P<0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (r = −0.644, P = 0.024). These observations may bring new hints to elaborate the pathogenesis of EH.
The potential effects of the interactions between DNA methylation (CpG1 and CpG2-5 methylation levels) of the α-adducin (ADD1) gene promoter and ADD1 tagSNPs (tag single-nucleotide polymorphisms) or the environmental factors on essential hypertension (EH) risk have not been clarified. Thus, we performed an age- and gender-matched case-control study to investigate the association between ADD1 tagSNPs and EH. A total of 1020 subjects with EH and 1020 normotensive subjects were genotyped by melting temperature shift technology. Logistic regression was used to assess the associations of ADD1 tagSNPs, environmental factors and EH. The generalized multifactor dimensionality reduction (GMDR) method was applied to explore the potential interactions. Under additive, dominant and recessive models, no significant associations were evidenced between EH and rs3755885, rs2071694, rs4963 or rs3775067 with the complete data set or the gender-stratified analysis after adjusting for triglycerides, body mass index and alcohol consumption. However, we observed a significant association between rs4961 and EH under the dominant model after Bonferroni correction when adjusting for confounding factors in the entire sample (odds ratio (OR)=0.64, 95% confidence interval (CI)=0.50-0.83, P=0.001). In GMDR, the two-factor interaction model of alcohol consumption and DNA methylation (CpG1 methylation) was the best model, with a maximum cross-validation consistency of 9/10 and testing balance accuracy of 0.63 (P=0.01). Our results indicate that the SNP rs4961 has a protective role in the development of EH. In conclusion, the interactions between alcohol consumption and DNA methylation (CpG1 methylation) of the ADD1 gene promoter have a significant role in modifying EH susceptibility.
Abstract. Essential hypertension (EH) is commonlyaccompanied by a dysfunction of glucose metabolism. Glucokinase (GCK) is a key enzyme involved in glucose metabolism. The aim of the present study was to investigate whether GCK gene-body methylation contributed to the risk of EH. A total of 47 patients with EH and 47 age-matched controls were recruited for methylation research in the current study. GCK gene-body methylation was measured using bisulphite pyrosequencing technology. DNA methylation levels were closely correlated among CpG1, CpG2 and CpG3 (r>0.70; P<0.001), in contrast with a weaker correlation between CpG4 and the preceding three CpGs (r<0.3 or r=1; P>0.05). Significantly lower CpG1-3 methylation (cases vs. controls, 49.13±5.72 vs. 53.49±7.53%; adjusted P= 0.006) and significantly higher CpG4 methylation (cases vs. controls, 46.34±6.48 vs. 34.74±12.73%; adjusted P=0.002) were observed in patients with EH. The present study indicated that aberrant methylation of the GCK gene body was significantly associated with the risk of EH in the population assessed. The discrepancies between CpG1-3 and CpG4 methylation may suggest distinct roles for each of them in the determination of the risk of EH.
The amiloride-sensitive sodium channel beta subunit (SCNN1B) gene encodes the beta subunit of the epithelial sodium channel, which is involved in blood pressure homeostasis. The aim of the present study was to investigate the association between SCNN1B gene promoter methylation and essential hypertension (EH), and to explore whether SCNN1B methylation was altered by antihypertensive therapy. The present study recruited 282 individuals: 94 controls, 94 incident cases and 94 prevalent cases. Subsequently, the methylation status of six CpG sites in the SCNN1B promoter region was measured using bisulfite pyrosequencing technology. Among the six CpG sites, a significant difference in CpG1 and CpG2 methylation levels were detected between controls and incident cases (CpG1: β‑standardized=0.17, adjusted P=0.015; CpG2: β‑standardized=‑0.41, adjusted P=0.001). In addition, a significant difference was detected in CpG1 methylation levels between incident cases and prevalent cases (β‑standardized=‑0.252, adjusted P=3.77E‑04). The present study also demonstrated that CpG1 and CpG2 methylation levels were significantly lower in males compared with in females (CpG1: t=‑3.180, P=0.002; CpG2: t=‑2.148, P=0.033). CpG1 methylation was also shown to be positively correlated with age (controls: r=0.285, P=0.008; incident cases: r=0.401, P=0.0001; prevalent cases: r=0.367, P=0.001). These results indicated a significant association between EH and SCNN1B methylation, which was affected by age, gender and antihypertensive therapy.
Coronary artery disease (CAD) has become the main cause of mortality worldwide. Lectin galactoside-binding soluble-2 () is involved in the cytokine lymphotoxin-α (LTA) cascade that may influence the progress of CAD. The aim of the present study was to assess the association between the 3279C>T (rs7291467) polymorphism and CAD. A total of 562 cases and 572 controls were recruited to examine the association. A systematic meta-analysis was performed to evaluate the contribution of 3279C>T polymorphism to the risk of CAD among 12,093 cases and 11,020 controls. There was no significant association found in the present case-control study. However, the meta-analysis showed that 3279C>T played a protective role in CAD [P=0.008, odds ratio (OR), 0.90; 95% confidence interval (95% CI), 0.82-0.97] and particularly in the Asian population (P=0.006; OR, 0.82; 95% CI, 0.71-0.94). The present case-control study did not find a significant association between 3279C>T and CAD in the Eastern Han Chinese population. However, the meta-analysis indicated that 3279C>T played a protective role in CAD, suggesting an ethnic difference in the association of the locus with CAD.
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