Work

Determination of methylated CpG sites in the promoter region of catechol-O-methyltransferase (COMT) and their involvement in the etiology of tobacco smoking

Year: 2010
Type: article
Study design: Observational Study
Abstract: We previously reported that catechol-O-methyltransferase (COMT) is significantly associated with nicotine dependence (ND) in humans. In this study, we examined whether there exists any difference in the extent of methylation of CpG dinucleotides in the promoter region of COMT in smokers and non-smokers by analyzing the methylation status of cytosines at 33 CpG sites through direct sequencing of bisulfite-treated DNA (N = 50 per group). The cytosine was methylated at 13 of 33 CpG sites, and two of these sites showed significant differences between smokers and matched non-smoker controls. Specifically, in the -193 CpG site, the degree of methylation was 19.1% in smokers and 13.2% in non-smokers (P < 0.01). This finding was confirmed by methylation-specific PCR using an additional 100 smoker and 100 non-smoker control samples, which showed the degree of methylation to be 22.2% in smokers and 18.3% in non-smokers (P < 0.01). For the -39 CpG site, the degree of methylation was 9.2% in smokers, whereas no methylation was found in non-smoker controls. Together, our findings provide the first molecular explanation at the epigenetic level for the association of ND with methylation of the COMT promoter, implying that methylation plays a role in smoking dependence.
Author: Qing Xu
Language: English
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W2069492893
FWCI: 0.956
Cites: 50
Cited by: 33
Related to: 10