Please cite this article as follows: Numata S, Iga J-i, Nakataki M, Tayoshi S, Taniguchi K, Sumitani S, Tomotake M, Tanahashi T, Itakura M, Kamegaya Y, Tatsumi M, Sano A, Asada T, Kunugi H, Ueno S-i, Ohmori T. 2008. Gene Expression and Association Analyses of the Phosphodiesterase 4B (PDE4B) Gene in Major Depressive Disorder in the Japanese Population. Am J Med Genet Part B 150B:527–534.
Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population†
Article first published online: 10 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 4, pages 527–534, 5 June 2009
How to Cite
Numata, S., Iga, J.-i., Nakataki, M., Tayoshi, S., Taniguchi, K., Sumitani, S., Tomotake, M., Tanahashi, T., Itakura, M., Kamegaya, Y., Tatsumi, M., Sano, A., Asada, T., Kunugi, H., Ueno, S.-i. and Ohmori, T. (2009), Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population. Am. J. Med. Genet., 150B: 527–534. doi: 10.1002/ajmg.b.30852
- Issue published online: 18 MAY 2009
- Article first published online: 10 SEP 2008
- Manuscript Accepted: 28 JUL 2008
- Manuscript Received: 23 MAY 2008
- Japanese Ministry of Health, Labor and Welfare
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- 21st Century COE program
- Human Nutritional Science on Stress Control, Tokushima, Japan
- association analysis;
- expression analysis;
- major depressive disorder;
- peripheral blood leukocytes
The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD. © 2008 Wiley-Liss, Inc.