Lower ADD1 gene promoter DNA methylation increases the risk of essential hypertension.
PLoS One
; 8(5): e63455, 2013.
Article
em En
| MEDLINE
| ID: mdl-23691048
ABSTRACT
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 Pâ=â0.016; CpG2-5 Pâ=â0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted Pâ=â0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted Pâ=â0.008). CpG1 methylation was inversely correlated with age in females (râ=â-0.407, Pâ=â0.019) 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 Pâ=â0.006; CpG2-5 Pâ=â0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age Pâ=â0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC)â=â0.855, Pâ=â0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUCâ=â0.699, Pâ=â0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, Pâ=â0.001), aspartate aminotransferase (AST, Pâ=â0.005) and uric acid (P<0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (râ=â-0.644, Pâ=â0.024). These observations may bring new hints to elaborate the pathogenesis of EH.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
/
Metilação de DNA
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Proteína de Ligação a Elemento Regulador de Esterol 1
/
Hipertensão
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article