A longitudinal study of the association between the GNB3 C825T polymorphism and metabolic disturbance in bipolar II patients treated with valproate

Chen, P. S.; Chang, Hern-Jia; Huang, Chun-Wei; Lee, C. C.; Lee, S. Y.; Huang, San Yuan; Yang, Yen Kuang; Lu, Ru Band

doi:10.1038/tpj.2015.96

Cited by 10 publications

(6 citation statements)

References 60 publications

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“…In addition, obesity in women with BD may be a side effect of mood stabilizers. Many studies have also confirmed the association between long‐term treatments of valproate and elevated risk of obesity, weight gain, type 2 diabetes, and dyslipidemia (P. S. Chen et al, ; Petty et al, ; Rehman, Sachan, & Chitkara, ; Verrotti, la Torre, Trotta, Mohn, & Chiarelli, ). Another study found the sex‐related pharmacokinetic differences of valproate, showing that valproate‐treated women without contraceptive therapy have longer lag times, lower hepatic outputs, and higher reabsorbed fraction than men (Ibarra, Vázquez, Fagiolino, & Derendorf, ).…”

Section: Discussionmentioning

confidence: 89%

“…In addition, obesity in women with BD may be a side effect of mood stabilizers. Many studies have also confirmed the association between long-term treatments of valproate and elevated risk of obesity, weight gain, type 2 diabetes, and dyslipidemia (P. S. Chen et al, 2017;Petty et al, 2014;Rehman, Sachan, & Chitkara, 2017;Verrotti, la Torre, Trotta, Mohn, & Chiarelli, 2009).…”

Section: Discussionmentioning

confidence: 90%

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Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

Lin

Huang

et al. 2020

Human Psychopharmacology

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Objective Sex differences in bipolar disorder are well recognized but little attention has been paid to sex differences in homocysteine or hyperhomocysteinemia in bipolar patients. This study compared gender differences in homocysteine levels and rates of hyperhomocysteinemia in Chinese inpatients with bipolar disorder. Methods A total of 198 BD patients and 84 healthy controls were enrolled. The Young Mania Rating Scale, Hamilton Depression Rating Scale, and the Clinical Global Impressions–Severity scale were used to assess the affective symptomatology. Fasting plasma Hcy levels were measured by high‐performance liquid chromatography. Results Men had higher homocysteine levels than women and the prevalence of hyperhomocysteinemia in male patients was approximately twice that in female patients. Logistic regression analyses showed that HHcy was associated with less frequent use of valproate in males and being overweight in females. Further correlation analysis and multivariate regression analysis demonstrated that Hcy levels were inversely correlated with valproate treatment in men and positively associated with overweight in women. Conclusions In bipolar patients, there are significant differences between sexes in the levels of homocysteine and prevalence of hyperhomocysteinemia. This appears to be associated with lower prevalence of valproate prescribing in men and with being overweight in women.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 90%

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

Lin

Huang

et al. 2020

Human Psychopharmacology

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“…VPA is a clinically available drug for the treatment of epilepsy and bipolar disorder. VPA has been shown to block voltage-dependent sodium channels, to act as a histone deacetylase (HDAC) inhibitor, and to inhibit NFKB activation, which may affect the immune response [19]. Therefore, we examined the inhibitory effect of VPA on NFKB activity in IM-resistant GIST cells and a xenograft animal model.…”

Section: Resultsmentioning

confidence: 99%

Nuclear KIT induces a NFKBIB-RELA-KIT autoregulatory loop in imatinib-resistant gastrointestinal stromal tumors

et al. 2019

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Gastrointestinal stromal tumors (GISTs) are frequently driven by auto-activated, mutant KIT and have durable response to KIT tyrosine kinase inhibitor. However, acquired resistance is an increasing clinical issue in GIST patients receiving front-line imatinib therapy. Our previous studies showed the colocalization of KIT with DAPI-stained nuclei in GIST cells without knowing the role of nuclear KIT in GIST tumorigenesis. In this article, we first identified the binding of nuclear KIT to the promoter of NFKB inhibitor beta (NFKBIB) by chromatin immunoprecipitation (ChIP) sequencing and ChIP assays, which was accompanied with enhanced NFKBIB protein expression in GIST cells. Clinically, high NCCN risk GISTs had significantly higher mean expression levels of nuclear phospho-KIT and NFKBIB as compared with those of intermediate or low/very low-risk GISTs. Conversely, downregulation of NFKBIB by siRNA led to RELA nuclear translocation that could bind to the KIT promoter region and subsequently reduced KIT transcription/expression and the viability of GIST cells. These findings were further confirmed by either RELA overexpression or NFKB/RELA inducer, valproic acid, treatment to result in reduced KIT expression and relative cell viability of imatinib-resistant GIST cells. Combining valproic acid with imatinib showed significantly better growth inhibitory effects on imatinib-resistant GIST48 and GIST430 cells in vitro, and in the GIST430 animal xenograft model. Taken together, these results demonstrate the existence of a nuclear KIT-driven NFKBIB-RELA-KIT autoregulatory loop in GIST tumorigenesis, which are potential targets for developing combination therapy to overcome imatinib-resistant of KIT-expressing GISTs.

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“…In bipolar populations, VPA response showed a positive association with XBP1-116 C/G polymorphism, but replication is needed (Kim et al 2009). GNB3 variants have also been associated with metabolic abnormalities in cross-over (Chang et al 2010) and prospective studies (Chen et al 2017) of BD patients treated with VPA.…”

Section: Valproic Acidmentioning

confidence: 99%

Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection

Cuellar‐Barboza

McElroy

Veldić

et al. 2020

Int J Bipolar Disord

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Background: Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/ adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations. Main body: We searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information. Conclusions: The complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.

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A longitudinal study of the association between the GNB3 C825T polymorphism and metabolic disturbance in bipolar II patients treated with valproate

Cited by 10 publications

References 60 publications

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

Nuclear KIT induces a NFKBIB-RELA-KIT autoregulatory loop in imatinib-resistant gastrointestinal stromal tumors

Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection

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