Journal article
Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.136B(1), pp.58-61
07/05/2005
DOI: 10.1002/ajmg.b.30185
PMID: 15858822
Abstract
The serotonin transporter (5HTT; chromosomal location 17q12) is an important regulator of serotonergic neurotransmission and is the site of action for a number of antidepressant medications. Sequence variation at a VNTR known as the 5HTTLPR, which is 1.4 kb upstream of the translation start of 5HTT, has been associated in some studies with increased vulnerability to depression, neuroticism, and autism. Support for these clinical observations has included laboratory findings that 5HTTLPR variation is associated with changes in 5HTT gene translation. We re-examined these earlier laboratory findings by directly measuring 5HTT mRNA levels and genotyping four loci spanning the 5HTT gene using RNA and DNA prepared from 85 independent lymphoblast cell lines. Using this data, haplotypes were inferred and the resulting single point and haplotypes data analyzed by univariate and regression analyses. Consistent with the original findings, we found a significant effect of the 5HTTLPR on mRNA production. In contrast to previous reports, the effect on 5HTT mRNA production appeared to be mediated through an additive, not dominant, mechanism. Neither genotype nor haplotype at three other 5HTT loci were associated with alterations in mRNA production, although the small number of samples homozygous for the three most common haplotypes limits these findings. We conclude that further examination of the role of 5HTT sequence variation in regulating 5HTT mRNA production is warranted.
Details
- Title: Subtitle
- Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription
- Creators
- Sarah L Bradley - Department of Psychiatry, The University of Iowa, Rm 2-126 MEB Psychiatry Research/MEB, Iowa City, 52242, USAKaterina DodelzonHarinder K SandhuRobert A Philibert
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.136B(1), pp.58-61
- DOI
- 10.1002/ajmg.b.30185
- PMID
- 15858822
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Publisher
- United States
- Grant note
- DA015789-01 / NIDA NIH HHS K08MH064714 / NIMH NIH HHS
- Language
- English
- Date published
- 07/05/2005
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003424402771
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