Genotype Distributions and Allele Frequencies of Possible Major Depressive Disorder-Associated Single Nucleotide Polymorphisms, Cyclic Adenosine Monophosphate Response Element Binding Protein 1 rs4675690 and Piccolo rs2522833, in a Japanese Population

Abstract

It is known that the onset of major depressive disorder (MDD) would be associated with genetic factors. To investigate the susceptibility to psychiatric disorders, e.g. MDD, schizophrenia etc., it is necessary to compare the genetic differences of objective polymorphisms between in patients and in relative contol subjects. Recently, an increasing number of studies focused on the role of cyclic adenosine monophosphate response element binding protein 1 (CREB1) and Piccolo (PCLO) on MDD. However, there was no report about genetic characterization of polymorphisms in between MDD patients and healthy subjects in Japanese population. We analized genotype distributions and allele frequencies of CREB1 rs4675690 and PCLO rs2522833 polymorphisms in 267 Japanese subjects, respectively. In CREB1 rs4675690, C allele frequency (0.41) was lower than T allele (0.59). While in PCLO rs2522833, A allele frequency (0.45) was lower than C allele (0.55). Our findings may be useful for investigating the genetic factors concerning the susceptibility to MDD in Japanese population.Key words cAMP response element binding protein 1; Piccolo; polymorphism; Japanese; major depressive disorder Major depressive disorder (MDD) is a familial disorder and its familiarity mostly or entirely results from genetic influence.1) To investigate disease susceptibility affected by genetic polymorphism, it is often performed with comparison of genotype distributions and allele frequencies of objective polymorphism in patients with in its relative control subjects.Recently, an increasing number of studies focused on the role of transcription factor, cyclic adenosine monophosphate response element binding protein 1 (CREB1) and presynaptic cytomatrix protein, Piccolo (PCLO) on MDD. CREB1 was reported that the association with neuronal signal transduction involved in synaptic plasticity 2) and antidepressant response. 3,4) In Caucasian population, CREB1 rs4675690 polymorphism was associated with anger expression in male MDD patients 5) and suicidal behaivor in MDD patients. 6) While PCLO was localized in the presynaptic active zone 7) and involved in monoamine neurotransmission.8) PCLO polymorphism rs2522833 was related with hypothalamic-pituitary-adrenocortical (HPA) regulation during antidepressant treatment and the susceptibility to MDD in Caucasian population. 9)It was suggested that these polymorphisms may be associated with the susceptibility to MDD and therapeutic efficacy of antidepressants in Japanese population. However there was no report about CREB1 rs4675690 and PCLO rs2522833 polymorphisms in Japanese population. In this study, we examined genotype distributions and allele frequencies of CREB1 rs4675690 and PCLO rs2522833 polymorphisms in 267 Japanese healthy subjects. MATERIALS AND METHODS Japanese SubjectsThis study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and approved by the Ethics Committee of the University of Shizuoka, Shizuoka, Japan (approved number 18-2). A total of 267 Japanese...

PCLO rs2522833-mediated gray matter volume reduction in patients with drug-naive, first-episode major depressive disorder

“… 6 In the Japanese population, the frequency of carriers of the rs2522833 C-allele (that is, those with an A/C or a C/C genotype) is larger than that of A/A individuals. 7 A series of studies by Woudstra et al demonstrated that the PCLO C-allele increases the vulnerability of an individual to develop MDD by regulating regional brain function that responds to salient stimulation and processes negative information. 8 , 9 Ryan et al 10 recently reported that PCLO rs2522833 was also associated with the volume of the gray matter (GM), and to a lesser extent with hippocampal volume and white matter lesions in patients with late-life MDD.…”

Influence of Genetic Polymorphisms and Concomitant Anxiolytic Doses on Antidepressant Maintenance Doses in Japanese Patients with Depression

“…The presence of the CREB1 rs4675690 polymorphism was determined by allele-specific PCR as previously reported 21) ( Table 3). In brief, genomic DNA (100 ng) was amplified in a PCR buffer containing dNTP mixture (200 µM), forward primer (1 µM), allele-specific reverse primer (1 µM), 1.5 mM MgCl 2 , and HotStar Taq plus DNA polymerase (1.25 units).…”

New Insights Regarding Diagnosis and Medication for Schizophrenia Based on Neuronal Synapse–Microglia Interaction

“…Genome-wide association studies (GWASs) are important tools for elucidating the mechanisms underlying schizophrenia, including the formation of diseases. The dopamine hypothesis, the current leading theory of the pathogenesis of schizophrenia [ 4 , 5 ], is supported by genetic studies indicating that single nucleotide variations (SNVs) related to dopaminergic transmission, such as DRD2 [ 6 ], COMT [ 7 ], DISC1 [ 8 ], and PCLO [ 9 , 10 , 11 ], are associated with a higher risk of schizophrenia [ 5 , 12 ]. The GWAS conducted by the Schizophrenia Working Group of the Psychiatric Genomics Consortium has had a notable impact on the study of schizophrenia [ 13 ].…”