Journal article
The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.147B(5), pp.543-549
07/05/2008
DOI: 10.1002/ajmg.b.30657
PMCID: PMC3643119
PMID: 17987668
Abstract
Serotonin Transporter (
5HTT
or
SLC6A4
) mRNA transcription is regulated by both genetic and epigenetic mechanisms. Unfortunately, despite intense scrutiny, the exact identity and contribution of each of these regulatory mechanisms, and their relationship to behavioral illness remain unknown. This lack of knowledge is critical because alterations in
SLC6A4
function are posited to be central to a wide variety of CNS disorders. In order to address this shortcoming, we quantified 5HTTLPR genotype,
SLC6A4
mRNA production and CpG methylation using biomaterial from 192 lymphoblast cell lines derived from subjects who participated in the latest wave of the Iowa Adoption Studies. We then analyzed the resulting data with respect to clinical characteristics. We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the “Long G” allele on mRNA transcription. We also found that CpG methylation was higher (
P
< 0.0008) and mRNA production (
P
< 0.0001) was lower in females as compared to males. Those subjects with a lifetime history of Alcohol Dependence had higher levels of
SLC6A4
mRNA. There was a trend for an association of increased overall methylation with lifetime history of major depression. Finally, we confirm our prior findings that the exact levels of 5HTT mRNA expression are dependent on how it is measured. We conclude that both genetic variation and epigenetic modifications contribute to the regulation of
SLC6A4
function and that more in-depth studies of the molecular mechanisms controlling gene activity and the relationship of these mechanisms to behavioral illness are indicated.
Details
- Title: Subtitle
- The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies
- Creators
- Robert A Philibert - Department of Psychiatry, The University of Iowa, Iowa City, IowaHarinder Sandhu - Department of Psychiatry, The University of Iowa, Iowa City, IowaNancy Hollenbeck - Department of Psychiatry, The University of Iowa, Iowa City, IowaTracy Gunter - Department of Psychiatry, The University of Iowa, Iowa City, IowaWilliam Adams - Department of Psychiatry, The University of Iowa, Iowa City, IowaAnup Madan - The Institute for Systems Biology, Seattle, Washington
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.147B(5), pp.543-549
- DOI
- 10.1002/ajmg.b.30657
- PMID
- 17987668
- PMCID
- PMC3643119
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Language
- English
- Date published
- 07/05/2008
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070615902771
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