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Allele-specific expression and gene methylation in the control of CYP1A2 mRNA level in human livers
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
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2009 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 9, no 3, 208-217 p.Article in journal (Refereed) Published
Abstract [en]

The basis for interindividual variation in the CYP1A2 gene expression is not fully understood and the known genetic polymorphisms in the gene provide no explanation. We investigated whether the CYP1A2 gene expression is regulated by DNA methylation and displays allele-specific expression (ASE) using 65 human livers. Forty-eight percent of the livers displayed ASE not associated to the CYP1A2 mRNA levels. The extent of DNA methylation of a CpG island including 17 CpG sites, close to the translation start site, inversely correlated with hepatic CYP1A2 mRNA levels (P=0.018). The methylation of two separate core CpG sites was strongly associated with the CYP1A2 mRNA levels (P=0.005) and ASE phenotype (P=0.01), respectively. The CYP1A2 expression in hepatoma B16A2 cells was strongly induced by treatment with 5-aza-2'-deoxycytidine. In conclusion, the CYP1A2 gene expression is influenced by the extent of DNA methylation and displays ASE, mechanisms contributing to the large interindividual differences in CYP1A2 gene expression.

Place, publisher, year, edition, pages
2009. Vol. 9, no 3, 208-217 p.
Keyword [en]
CYP1A2, drug-metabolizing enzyme, gene expression, allele-specific expression, epigenetics, DNA methylation
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-120577DOI: 10.1038/tpj.2009.4ISI: 000266567100008PubMedID: 19274061OAI: oai:DiVA.org:uu-120577DiVA: diva2:303619
Available from: 2010-03-15 Created: 2010-03-15 Last updated: 2012-04-13Bibliographically approved

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Syvänen, Ann-Christine
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