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

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 po...

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Bibliographic Details
Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2007-01, Vol.144B (1), p.101-105
Main Authors: Philibert, Robert, Madan, Anup, Andersen, Allan, Cadoret, Remi, Packer, Hans, Sandhu, Harinder
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Cell Line
CpG Islands
DNA Methylation
DNA, Complementary - genetics
Epigenesis, Genetic
epigenetics
Exons
Genetics, Behavioral
Genotype
Humans
Medical genetics
Medical sciences
methylation
Molecular Sequence Data
promoter
Promoter Regions, Genetic
RNA, Messenger - genetics
RNA, Messenger - metabolism
Serotonin Plasma Membrane Transport Proteins - genetics
serotonin transporter
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Summary: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. © 2006 Wiley‐Liss, Inc.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.30414