title: Aberrant promoter methylation profile of Niemann-pick type C1 gene in cardiovascular disease.
abstract: The protein of Niemann-pick type C1 (NPC1) gene promotes the egress of cholesterol from late endosomes and lysosomes to other cellular compartments and contributes to a process known as reverse cholesterol transport. This study aimed to examine whether promoter methylation of NPC1 is associated with risk of cardiovascular disease (CVD).
  
  
  
  Fifty CVD patients and 50 healthy subjects as the control group were recruited in this study. Promoter methylation of NPC1 gene was defined using a nested-methylation specific polymerase chain reaction method. Statistical analyses were done using the chi-square, t-test or ANOVA tests.
  
  
  
  Our study showed that the frequency of semi-methylated promoter (methylated/unmethylated status) was significantly higher in CVD patients than that in controls (OR = 6.521, 95% CI = 2.211-19.215, P = 0.008). However, a completely methylated promoter (methylated/methylated status) was not detected in any subjects in either of the two groups tested. Additionally, the analysis of clinical data according to the methylation status of NPC1 gene demonstrated that serum levels of total cholesterol, total triglycerides, high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) are influenced by NPC1 methylation, so that subjects with a completely unmethylated promoter (Unmethylated/unmethylated status) held lower levels of total triglycerides, total cholesterol, LDL-C and higher levels of HDL-C.
  
  
  
  Our findings propose that the NPC1 promoter methylation is a probable mechanism that can result in reduced/impaired NPC1 expression/activity and may thus contribute to progression of CVD.
authors.affiliation: Dept. of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Afzali
authors.affiliation: Dept. of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.|Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nakhaee
authors.affiliation: Dept. of Cardiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Seyed Payman
authors.initials: SP
authors.lastname: Tabatabaei
authors.affiliation: Dept. of Anesthesia, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Tirgar-Fakheri
authors.affiliation: Dept. of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.|Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D000077296:Niemann-Pick C1 Protein; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein
keywords: Niemann-pick type C1; Promoter methylation; cardiovascular disease