A follow‐up case–control association study of tractable (druggable) genes in recurrent major depression

Schosser, Alexandra; Gaysina, Darya; Cohen‐Woods, Sarah; Domenici, Enrico; Perry, Julia; Tozzi, Federica; Korszun, Ania; Gunasinghe, Cerisse; Gray, Joanna; Jones, L. A.; Binder, Elke; Holsboer, Florian; Craddock, Nick; Craig, Ian W.; Farmer, Anne; Muglia, Pierandrea; McGuffin, Peter

doi:10.1002/ajmg.b.31204

Cited by 19 publications

(13 citation statements)

References 48 publications

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“…Although 2 out of 16 SNPs examined in a study of the human SLC4A10 gene locus were initially linked to major depressive disorder, the linkage was found to be not significant upon further statistical analysis (846).…”

Section: D) Defective Csf Secretion In Mice With a Disrupted Slc4a10 mentioning

confidence: 95%

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

Parker

Boron

2013

Physiological Reviews

248

262

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The mammalian Slc4 (Solute carrier 4) family of transporters is a functionally diverse group of 10 multi-spanning membrane proteins that includes three Cl-HCO3 exchangers (AE1-3), five Na(+)-coupled HCO3(-) transporters (NCBTs), and two other unusual members (AE4, BTR1). In this review, we mainly focus on the five mammalian NCBTs-NBCe1, NBCe2, NBCn1, NDCBE, and NBCn2. Each plays a specialized role in maintaining intracellular pH and, by contributing to the movement of HCO3(-) across epithelia, in maintaining whole-body pH and otherwise contributing to epithelial transport. Disruptions involving NCBT genes are linked to blindness, deafness, proximal renal tubular acidosis, mental retardation, and epilepsy. We also review AE1-3, AE4, and BTR1, addressing their relevance to the study of NCBTs. This review draws together recent advances in our understanding of the phylogenetic origins and physiological relevance of NCBTs and their progenitors. Underlying these advances is progress in such diverse disciplines as physiology, molecular biology, genetics, immunocytochemistry, proteomics, and structural biology. This review highlights the key similarities and differences between individual NCBTs and the genes that encode them and also clarifies the sometimes confusing NCBT nomenclature.

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Section: D) Defective Csf Secretion In Mice With a Disrupted Slc4a10 mentioning

confidence: 95%

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

Parker

Boron

2013

Physiological Reviews

248

262

View full text Add to dashboard Cite

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“…Interestingly, partial deletion of SLC4A10 has also been associated to autism (289). Association between gene variations in SLC4A10 and open-angle glaucoma (198) (which is dependent on CSF production) and major depression (284) were investigated, but no convincing association was found. Interestingly, in the choroid plexus of slc4a10 knockout mice, NHE1 is abnormally expressed in the basolateral membranes, whereas in the wild type mice, this transporter is located to the apical membrane (83).…”

Section: The Postcloning Eramentioning

confidence: 99%

Cation‐Coupled Bicarbonate Transporters

Aalkjær

Boedtkjer

Choi

et al. 2014

Comprehensive Physiology

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Cation-coupled HCO3− transport was initially identified in the mid-1970s when pioneering studies showed that acid extrusion from cells is stimulated by CO2/HCO3− and associated with Na+ and Cl− movement. The first Na+-coupled bicarbonate transporter (NCBT) was expression-cloned in the late 1990s. There are currently five mammalian NCBTs in the SLC4-family: the electrogenic Na,HCO3-cotransporters NBCe1 and NBCe2 (SLC4A4 and SLC4A5 gene products); the electroneutral Na,HCO3-cotransporter NBCn1 (SLC4A7 gene product); the Na+-driven Cl,HCO3-exchanger NDCBE (SLC4A8 gene product); and NBCn2/NCBE (SLC4A10 gene product), which has been characterized as an electroneutral Na,HCO3-cotransporter or a Na+-driven Cl,HCO3-exchanger. Despite the similarity in amino acid sequence and predicted structure among the NCBTs of the SLC4-family, they exhibit distinct differences in ion dependency, transport function, pharmacological properties, and interactions with other proteins. In epithelia, NCBTs are involved in transcellular movement of acid-base equivalents and intracellular pH control. In nonepithelial tissues, NCBTs contribute to intracellular pH regulation; and hence, they are crucial for diverse tissue functions including neuronal discharge, sensory neuron development, performance of the heart, and vascular tone regulation. The function and expression levels of the NCBTs are generally sensitive to intracellular and systemic pH. Animal models have revealed pathophysiological roles of the transporters in disease states including metabolic acidosis, hypertension, visual defects, and epileptic seizures. Studies are being conducted to understand the physiological consequences of genetic polymorphisms in the SLC4-members, which are associated with cancer, hypertension, and drug addiction. Here, we describe the current knowledge regarding the function, structure, and regulation of the mammalian cation-coupled HCO3− transporters of the SLC4-family.

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“…This gene is located on chromosome 2q24 and is highly expressed in the hippocampus and cerebral cortex. It has been implicated in complex partial epilepsy and mental retardation [88] as well as being a subject of interest in recurrent major depression [89]. The bicarbonate sensitive pathway is the most important mechanism for active lithium influx into the cell [90].…”

Section: Pharmacogenetics Of Response To Lithiummentioning

confidence: 99%

Genetic Influences on Response to Mood Stabilizers in Bipolar Disorder

Rybakowski

2013

CNS Drugs

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Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder. The first representative of their family was lithium, still considered a prototype drug for the prevention of manic and depressive recurrences in bipolar disorder. Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers, which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine, which were introduced in the mid-1990s, form the second generation of such drugs. The response of patients with bipolar disorder to mood stabilizers has different levels of magnitude. About one-third of lithium-treated patients are excellent responders, showing total prevention of the episodes, and these patients are clinically characterized by an episodic clinical course, complete remission, a bipolar family history, low psychiatric co-morbidity and a hyperthymic temperament. It has been suggested that responders to carbamazepine or lamotrigine may differ clinically from responders to lithium. The main phenotype of the response to mood stabilizers is a degree of prevention against recurrences of manic and depressive episodes during long-term treatment. The most specific scale in this respect is the so-called Alda scale, where retrospective assessment of lithium response is scored on a 0–10 scale. The vast majority of data on genetic influences on the response to mood stabilizers has been gathered in relation to lithium. The studies on the mechanisms of action of lithium and on the neurobiology of bipolar disorder have led to the identification of a number of candidate genes. The genes studied for their association with lithium response have been those connected with neurotransmitters (serotonin, dopamine and glutamate), second messengers (phosphatidyl inositol [PI], cyclic adenosine-monophosphate [cAMP] and protein kinase C [PKC] pathways), substances involved in neuroprotection (brain-derived neurotrophic factor [BDNF] and glycogen synthase kinase 3-β [GSK-3β]) and a number of other miscellaneous genes. There are no published pharmacogenomic studies of mood stabilizers other than lithium, except for one study of the X-box binding protein 1 (XBP1) gene in relation to the efficacy of valproate. In recent years, a number of genome-wide association studies (GWAS) in bipolar disorders have been performed and some of those have also focused on lithium response. They suggest roles for the glutamatergic receptor AMPA (GRIA2) gene and the amiloride-sensitive cation channel 1 neuronal (ACCN1) gene in long-term lithium response. A promise for better elucidating the genetics of lithium response has been created by the formation of the Consortium on Lithium Genetics (ConLiGen) to establish the largest sample, to date, for the GWAS of lithium response in bipolar disorder. The sample currently comprises more than 1,200 patients, characterized by their response to lithium treatment according to the Alda scale. Preliminary results from this international stud...

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A follow‐up case–control association study of tractable (druggable) genes in recurrent major depression

Cited by 19 publications

References 48 publications

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

Cation‐Coupled Bicarbonate Transporters

Genetic Influences on Response to Mood Stabilizers in Bipolar Disorder

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