skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8838

Association of PDE11A global haplotype with major depression and antidepressant drug response

Original Research

(2022) Views  (605) Full article downloads

Authors: Huai-Rong Luo, Gui-Sheng Wu, Chuanhui Dong, Mauricio Arcos-Burgos, et al.

Published Date March 2009 Volume 2009:5 Pages 163 - 170
DOI: http://dx.doi.org/10.2147/NDT.S4771

Huai-Rong Luo, Gui-Sheng Wu, Chuanhui Dong, Mauricio Arcos-Burgos, Luciana Ribeiro, Julio Licinio, Ma-Li Wong

Center on Pharmacogenomics, Department of Psychiatry and Behavioral Science, University of Miami Miller School of Medicine, Miami, FL, USA

Abstract: Cyclic nucleotide phosphodiesterases (PDEs) hydrolyze the intracellular second messengers cAMP and cGMP to their corresponding monophosphates. PDEs play an important role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. We have previously shown that the individual haplotype GAACC in the PDE11A gene was associated with major depressive disorder (MDD) based on block-by-block analysis. There are two PDE genes, PDE11A and PDE1A, located in chromosome 2q31–q32. In this study, we have further explored whether the whole region 2q31–q32 contribute to MDD or antidepressant response 278 depressed Mexican-American participants and 321 matched healthy controls. Although there is no significant interaction between the two genes, the remission rate of individual carrying the combination genotype at rs1880916 (AG/AA) and rs1549870 (GG) is significantly increased. We analyzed the global haplotype by examining 16 single-nucleotide polymorphisms (SNPs) in PDE11A and six SNPs in PDE1A. None of the haplotypes consisting of six SNPs in the PDE1A have a significant difference between depressed and control groups. Among haplotypes consisting of 16 SNPs across 440 kb in the PDE11A gene, 18 common haplotypes (with frequency higher than 0.8%) have been found in the studied population. Six haplotypes showed significantly different frequencies between the MDD group and the control group. The phylogenetic network result for the 16 SNPs showed that several historic recombination events have happened in the PDE11A gene. The frequency of one haplotype is significantly lower in the remitter group than in the nonremitter group for the depressed participants treated with either desipramine or fluoxetine. Thus, our data suggest that the PDE11A global haplotype is associated with both MDD and antidepressant drug response.

Keywords: PDE11A, major depression, antidepressant, haplotype, linkage disequilibrium, recombination








Readers of this article also read:

Restless legs syndrome: differential diagnosis and management with rotigotine
Desvenlafaxine in the treatment of major depressive disorder
Differential clinical effects of fluvoxamine by the effect of age in Japanese female major depressive patients
Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors
Adenylate-cyclase activity in platelets of patients with obsessive-compulsive disorder
Coenzyme Q10 effects in neurodegenerative disease
Perception of risk and benefit in patient-centered communication and care
The relationship between deliberate self-harm behavior, body dissatisfaction, and suicide in adolescents: current concepts
Zinc oxide nanoparticles as selective killers of proliferating cells
Cumulative clinical experience from over a decade of use of levofloxacin in community-acquired pneumonia: critical appraisal and role in therapy