Gene expression and association analysis of LIM (PDLIM5) in major depression

Iga, Jun‐ichi; Ueno, Shu‐ichi; Yamauchi, Ken; Numata, Shusuke; Motoki, Ikuyo; Tayoshi, Sumiko; Kinouchi, Sawako; Ohta, Koshi; Song, Hongwei; Morita, Kyoko; Rokutan, Kazuhito; Tanabe, Hirotaka; Sano, Akira; Ohmori, Tetsuro

doi:10.1016/j.neulet.2006.02.044

Cited by 37 publications

(25 citation statements)

References 25 publications

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“…As the main affected organ in mental disorders, the brain, is not easily accessible in living subjects, a key issue in biological psychiatry is the search of peripheral biomarkers (Iga et al, 2006;Gavin and Sharma, 2010) for differential diagnosis and, mostly, for prediction of treatment response.…”

Section: Dna Methylation Of Bdnf Gene In Bipolar Disorder C D'addariomentioning

confidence: 99%

Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII

D’Addario

Dell’Osso

Palazzo

et al. 2012

Neuropsychopharmacol

163

109

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The etiology of bipolar disorder (BD) is still poorly understood, involving genetic and epigenetic mechanisms as well as environmental contributions. This study aimed to investigate the degree of DNA methylation at the promoter region of the brain-derived neurotrophic factor (BDNF) gene, as one of the candidate genes associated with major psychoses, in peripheral blood mononuclear cells isolated from 94 patients with BD (BD I ¼ 49, BD II ¼ 45) and 52 healthy controls. A significant BDNF gene expression downregulation was observed in BD II 0.53±0.11%; Po0.05), but not in BD I (1.13±0.19%) patients compared with controls (CONT: 1±0.2%). Consistently, an hypermethylation of the BDNF promoter region was specifically found in BD II patients (CONT: 24.0±2.1%; BDI: 20.4±1.7%; BDII: 33.3 ± 3.5%, Po0.05). Of note, higher levels of DNA methylation were observed in BD subjects on pharmacological treatment with mood stabilizers plus antidepressants (34.6 ± 4.2%, predominantly BD II) compared with those exclusively on mood-stabilizing agents (21.7 ± 1.8%; Po0.01, predominantly BD I). Moreover, among the different pharmacological therapies, lithium (20.1 ± 3.8%, Po0.05) and valproate (23.6 ± 2.9%, Po0.05) were associated with a significant reduction of DNA methylation compared with other drugs (35.6 ± 4.6%). Present findings suggest selective changes in DNA methylation of BDNF promoter in subjects with BD type II and highlight the importance of epigenetic factors in mediating the onset and/or susceptibility to BD, providing new insight into the mechanisms of gene expression. Moreover, they shed light on possible mechanisms of action of mood-stabilizing compounds vs antidepressants in the treatment of BD, pointing out that BDNF regulation might be a key target for their effects.

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Section: Dna Methylation Of Bdnf Gene In Bipolar Disorder C D'addariomentioning

confidence: 99%

Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII

D’Addario

Dell’Osso

Palazzo

et al. 2012

Neuropsychopharmacol

163

109

View full text Add to dashboard Cite

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“…Moreover, Kato et al (2005) provided confirmation of up-regulation of the mRNA level of PDLIM5 in an independent brain sample set obtained from the Stanley Array Collection. Recently, Iga et al (2006) reported the LIM mRNA expression levels in the peripheral leukocytes from drug-naive depressive patients were significant lower than those from control subjects in Japanese population.…”

Section: Introductionmentioning

confidence: 98%

Positive association between PDLIM5 and schizophrenia in the Chinese Han population

Tao

Qin

et al. 2008

International Journal of Neuropsychopharmacology

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The PDZ and LIM domain 5 protein (PDLIM5) contains one PDZ (post-synaptic density-95/discs large/zone occludens-1) domain and three LIM (Lin-11, Isl-1, and Mec-3) domains, and is also known as Enigma homologue LIM domain (ENH) protein or LIM protein. DNA microarray analysis of post-mortem brains of schizophrenics has indicated up-regulation of the mRNA level of PDLIM5, and Horiuchi and colleagues reported two single nucleotide polymorphisms (SNPs) (rs2433320 and rs2433322) in the 5' region of the PDZ and LIM domain 5 gene (PDLIM5) to be significantly associated with schizophrenia in the Japanese population. On the other hand, no association with schizophrenia was observed by Kato and colleagues in a different sample of the Japanese population. In this study, we genotyped six SNPs (including rs2433320 and rs2433322) covering PDLIM5 in 507 schizophrenia patients and 530 normal controls recruited from Jiangxi Province, China. Although rs2433320 was negative in our samples, rs2433322 showed significantly different frequencies between cases and controls (P=0.000010). In addition, high linkage disequilibrium was observed between rs2433320 and rs2433322 (D'=0.880), and haplotypes constructed from the two SNPs were significantly associated with schizophrenia (global P=0.00019, even after strict Bonferroni correction). Our results provide further evidence to support PDLIM5 as a potential susceptible gene for schizophrenia.

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“…This protein modulates neuronal calcium signaling by binding to specific voltage-gated calcium channels expressed in the axons [36], [62], [63]. Several studies have reported increased levels of basal calcium levels in blood samples from patients with bipolar disorder and it has been suggested that dysregulation of intracellular calcium homeostasis may be involved in controlling mood states in this disease [36].…”

Section: Discussionmentioning

confidence: 99%

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

2012

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Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations. A link between hormone signaling and these mood disorders has, therefore, been suggested to exist in many studies. Estrogen, one of the primary female sex hormones, mediates its effect mostly by binding to estrogen receptors (ERs). Nuclear ERs function as transcription factors and regulate gene transcription by binding to specific DNA sequences. A nucleotide change in the binding sequence might alter the binding efficiency, which could affect transcription levels of nearby genes. In order to investigate if variation in ER DNA-binding sequences may be involved in mood disorders, we conducted a genome-wide study of ER DNA-binding in patients diagnosed with major depression or bipolar disorder. Association studies were performed within each gender separately and the results were corrected for multiple testing by the Bonferroni method. In the female bipolar disorder material a significant association result was found for rs6023059 (corrected p-value = 0.023; odds ratio (OR) 0.681, 95% confidence interval (CI) 0.570–0.814), a single nucleotide polymorphism (SNP) placed downstream of the gene coding for transglutaminase 2 (TGM2). Thus, females with a specific genotype at this SNP may be more vulnerable to fluctuating estrogen levels, which may then act as a triggering factor for bipolar disorder.

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Gene expression and association analysis of LIM (PDLIM5) in major depression

Cited by 37 publications

References 25 publications

Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII

Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII

Positive association between PDLIM5 and schizophrenia in the Chinese Han population

Significant Association of Estrogen Receptor Binding Site Variation with Bipolar Disorder in Females

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