期刊
MOLECULAR PSYCHIATRY
卷 19, 期 8, 页码 880-889出版社
SPRINGERNATURE
DOI: 10.1038/mp.2013.126
关键词
ADHD; dopamine transporter; genetics; meta-analysis; PET; SPECT
资金
- National Institutes of Health (NIH)
- Shire
- Alcobra
- Otsuka
- McNeil
- Janssen
- Novartis
- Pfizer
- Eli Lilly
- Shire Laboratories Inc
- Shire Laboratories Inc, Cephalon
- Eli Lilly Company
- McNeil Pharmaceutical
- Novartis Pharmaceuticals
- Department of Defense
- Royalties and Licensing fees on copyrighted ADHD scales through MGH Corporate Sponsored Research and Licensing
- Harvard University
- Navidea Biopharmaceuticals
- Prexa Pharmaceuticals
- NIDA
- CDC
- NIDA Council
- Hilton Foundation and Convecta
- Elminda
- Fundacion Areces
- Medice Pharmaceuticals
- Spanish Child Psychiatry Association
- Abbott
- Alza
- AstraZeneca
- Bristol Myers Squibb
- Celltech
- Cephalon
- Eli Lilly and Co.
- Esai
- Glaxo
- Gliatech
- Merck
- NARSAD
- New River
- NICHD
- NIMH
- Noven
- Neurosearch
- Organon
- Pharmacia
- Prechter Foundation
- Stanley Foundation
- UCB Pharma, Inc.
- Wyeth
Much psychiatric genetic research has focused on a 40-base pair variable number of tandem repeats (VNTR) polymorphism located in the 30-untranslated region (30UTR) of the dopamine active transporter (DAT) gene (SLC6A3). This variant produces two common alleles with 9- and 10-repeats (9R and 10R). Studies associating this variant with in vivo DAT activity in humans have had mixed results. We searched for studies using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) to evaluate this association. Random effects meta-analyses assessed the association of the 30UTR variant with DAT activity. We also evaluated heterogeneity among studies and evidence for publication bias. We found twelve studies comprising 511 subjects, 125 from PET studies and 386 from SPECT studies. The PET studies provided highly significant evidence that the 9R allele was associated with increased DAT activity in human adults. The SPECT studies were highly heterogeneous. As a group, they suggested no association between the 30UTR polymorphism and DAT activity. When the analysis was limited to the most commonly used ligand, [123I] b-CIT, stratification by affection status dramatically reduced heterogeneity and revealed a significant association of the 9R allele with increased DAT activity for healthy subjects. In humans, the 9R allele of the 30UTR polymorphism of SLC6A3 regulates dopamine activity in the striatal brain regions independent of the presence of neuropsychiatric illness. Differences in study methodology account for the heterogeneous results across individual studies.
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