Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island

Robert Philibert; Anup Madan; Allan Andersen; Remi Cadoret; Hans Packer; Harinder Sandhu

doi:10.1002/ajmg.b.30414

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Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island

Journal article

Open access

Peer reviewed

Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island

Robert Philibert, Anup Madan, Allan Andersen, Remi Cadoret, Hans Packer and Harinder Sandhu

American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.144B(1), pp.101-105

01/05/2007

DOI: 10.1002/ajmg.b.30414

PMID: 16958039

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Abstract

The serotonin reuptake transporter (5HTT) is thought to be the principal regulator of serotonergic activity and epigenetic effects at this locus are thought to be important moderators of vulnerability to neuropsychiatric illness. In attempt to understand the basis of this regulation, several gene polymorphisms that affect 5HTT mRNA levels have been described. But to date, no clear mechanism linking these polymorphisms to vulnerability to epigenetic effects have been described. In this communication, we describe a CpG island in the 5' region of the 5HTT gene that contains an alternative exon 1 and possible promoter for 5HTT. We then confirm the existence of this transcript and ascertain the methylation status of this CpG island in 49 lymphoblast cell lines and analyze the relationship between methylation and 5HTT mRNA levels. We demonstrate that methylation at this CpG island is associated with decreased levels of 5HTT mRNA, but that this effect is evident only when 5HTTLPR genotype is taken into account. We suggest that these findings have significant implications for the understanding of the role of this locus in behavioral illness.

Cell Line

Promoter Regions, Genetic

Exons

Epigenesis, Genetic

Humans

RNA, Messenger - genetics

DNA, Complementary - genetics

Molecular Sequence Data

Genetics, Behavioral

Genotype

RNA, Messenger - metabolism

DNA Methylation

Serotonin Plasma Membrane Transport Proteins - genetics

Base Sequence

CpG Islands

Details

Title: Subtitle: Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island
Creators: Robert Philibert - Department of Psychiatry, The University of Iowa, Psychiatry Research/MEB, Iowa City, Iowa, USA. robert-philibert@uiowa.edu
Anup Madan
Allan Andersen
Remi Cadoret
Hans Packer
Harinder Sandhu
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.144B(1), pp.101-105
DOI: 10.1002/ajmg.b.30414
PMID: 16958039
NLM abbreviation: Am J Med Genet B Neuropsychiatr Genet
ISSN: 1552-4841
eISSN: 1552-485X
Publisher: United States
Grant note: K08MH064714 / NIMH NIH HHS R01AI053264 / NIAID NIH HHS R01DA015789 / NIDA NIH HHS
Language: English
Date published: 01/05/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003489902771

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