Journal article
Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.1
Molecular Neuropharmacology Group and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.2
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.3
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark and Research Unit for Psychiatric Rehabilitation, Mental Health Centre Ballerup, Ballerup, Denmark.4
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark.5
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark.6
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark.7
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.8
Center for Integrated Molecular Brain Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.9
Mental Health Centre Amager, Copenhagen, Denmark.10
...and 0 moreThere is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression.
Our study aimed at replicating this association in a large Danish population with major depression. Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro.
In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5%, n = 593; p = 0.009; odds ratio, OR: 1.46) as compared to ethnically matched controls (3.8%, n = 2912), while schizophrenia patients (4.1%, n = 503) did not differ.
In vitro, the Pro7 substitution appeared to be associated with reduced levels of NPY without affecting its mRNA level. The Leu7Pro variation may increase the risk of major depression, possibly by affecting the biosynthesis of NPY.
| Language: | English |
|---|---|
| Publisher: | Cambridge University Press (CUP) |
| Year: | 2012 |
| Pages: | 81-90 |
| ISSN: | 16015215 and 09242708 |
| Types: | Journal article |
| DOI: | 10.1111/j.1601-5215.2011.00600.x |
| ORCIDs: | Als, Thomas D , 0000-0002-6321-3850 , 0000-0001-9377-9436 , 0000-0003-1508-6866 and 0000-0002-0020-3807 |
