[Hypermethylation of estrogen receptor-alpha gene and high homocysteine in atheromatosis patients].
OBJECTIVE
To investigate the methylation status in promoter region of ER-alpha gene and the relationship beteen the degree of methylation in ER-alpha gene and the level of total plasma homocysteine(tHcy) in atherosclerosis patients.


METHODS
82 cases including 54 atherosclerosis patients and 28 healthy control subjects were selected under carotid colorized ultrasound examination. The methylation status of CpG islands in ER-alpha gene promoter region were analyzed by nested-methylation-specific PCR (nMSP). tHcy was examined by fluorescent-biochemical method. Using spearman rank correlation to analyse the relatinship between the degree of methylation in ER-alpha gene and the level of tHcy.


RESULTS
Hypermethylation of ER-alpha gene promoter region was found in 38 cases of atherosclerosis patients, the methylation frequency was 70.4%. While the only 28.6% methylation frequency was detected in healthy controls, just 8 of 28 samples were found hypermethylation, much lower than the one in atherosclerosis group (P < 0.05). Meanwhile, the level of tHcy in atherosclerosis group was significantly higher than that in control group (P < 0.05). The spearman rank correlation analysis explored an obviously correlation between the degree of methylation in ER-alpha gene and the level of tHcy (r = 0.809, P < 0.05), and the severity of atherosclerotic lesion was also heightened along with the increment of plasma level of tHcy.


CONCLUSIONS
Hyermethylation of CpG islands in ER-alpha gene promoter region was found in high frequency in atherosclerosis patients, which is positive correlated with the increased level of plasma tHcy and the severity of atherosclerotic lesion. This clinical data further extended our in vitro experimental result that HHcy can lead to the hypermethylation of ER-alpha gene, and hence to promote the occurrence and development of AS.
Zhi
Yanfang
Y
Department of Pathophysiology, College of Preclinical Medical and Forensic Medicines, Sichuan University, Chengdu 610041, China. zhiyanfang1980@126.com
Huang
Yansheng
Y
Li
Zhuhua
Z
Zhang
Ruiming
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics
D047628:Estrogen Receptor alpha; D006710:Homocysteine