title: [Methylation in Promoter Region of SLC6A2 Gene in Heart Failure Patients and Its Correlation with Qi Deficiency/Blood Stasis Syndrome].
abstract: OBJECTIVE
  To explore the methylation status in promoter region of norepinephrine transporter gene (NET, SLC6A2) in heart failure ( HF) patients and its correlation with qi deficiency/blood stasis syndrome (QDS/BSS).
  
  
  METHODS
  Thirty-six patients with heart failure (NYHA classification III to IV) were recruited in the study (as the heart failure group) and their scores of QDS/BSS were evaluated. Besides, a healthy elderly group (30 cases) and a healthy youth group (30 cases) were also set up. They were recruited from Physical Examination Center of Fujian Provincial Hospital. Pyrosequencing was applied to detect the methylation in promoter region of SLC6A2 gene, and the total methylation index (MTI) of CpG island was calculated. The correlation between the methylation status in promoter region of SLC6A2 and scores of QDS/BSS was assessed using Pearson and Partial analyses. Risk factors were screened and adjusted using Logistic regression.
  
  
  RESULTS
  By one-factor analysis of variance, the total MTI in the HF group (219.72% ± 54.03%) was obviously higher than that in the healthy elderly group (194.47% ± 34.92%) and the healthy youth group (161.60% ± 41.11%) (all P < 0.05). Meanwhile, the total MTI was higher in the healthy elderly group than in the healthy youth group (P < 0.01). By covariance analysis , after controlling age and BMI, the total MTI was higher in the HF group than in the healthy elderly group (P = 0.041), while it was higher in the healthy elderly group than in the healthy youth group (P = 0.016). Age was found to play an essential role in affecting MTI of SLC6A2 gene promoter region among the 3 groups (F = 16.447, P = 0.01). The total MTI was quite lower in the healthy youth group. Results of Partial correlation analysis showed MTI was positively correlated with scores of qi deficiency and blood stasis respectively (r = 0.494 and 0.419 respectively, both P < 0.05). Logistic regression analysis showed after adjusting confounding factors, the relative risk (OR value) of total MTI of SLC6A2 gene in promoter region was 1.038 (95% CI, 1.006 to 1.071, P = 0.020).
  
  
  CONCLUSIONS
  Abnormally elevated methylation of the promoter region of SLC6A2 gene is one of risk factors for HF. In addition, the degree of methylation of the promoter region of SLC6A2 gene was positively correlated with the severity of QDS/BSS.
authors.forename: Jie-wei
authors.initials: JW
authors.lastname: Luo
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Meng
authors.forename: Fang-meng
authors.initials: FM
authors.lastname: Huang
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Xing-yu
authors.initials: XY
authors.lastname: Zheng
authors.forename: Shi-chao
authors.initials: SC
authors.lastname: Wei
authors.forename: Miao-miao
authors.initials: MM
authors.lastname: Guo
authors.forename: Shi-ming
authors.initials: SM
authors.lastname: Wu
authors.forename: Hong-yi
authors.initials: HY
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000368:Aged; D019175:DNA Methylation; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D016015:Logistic Models; D008516:Medicine, Chinese Traditional; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D019413:Qi
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human