title: Pharmacogenetics of lithium effects on glomerular function in bipolar disorder patients under chronic lithium treatment: a pilot study.
abstract: Bipolar disorder (BD) is a psychiatric disease characterized by alternating episodes of mania and depression. Lithium (Li) represents the mainstay treatment for BD, although a significant proportion of patients shows insufficient or no response. Li is also associated with potentially severe side effects, including renal effects. Several studies reported that Li may induce reduction of glomerular filtration rate (GFR) in patients under long-term treatment. The biological systems and the genetic factors involved in susceptibility to Li-induced renal-side effects have been scarcely explored. The aim of our study was to test the contribution of putatively risk genetic variants in Li-induced reduction in estimated GFR (eGFR) in BD patients under long-term Li treatment. Tag SNPs, located in genes previously shown to be associated with kidney dysfunction or Li mechanism of action, were selected and genotyped in a sample of 70 BD patients of Sardinian origin. SNP rs378448, located in Acid Sensing Ion Channel Neurona-1 (ACCN1) gene, showed a significant interaction with duration of Li treatment on eGFR (F2=3.623, p=0.033). Our preliminary findings suggest that rs378448 could predispose BD subjects to a detrimental effect of chronic Li treatment on kidney functioning.
authors.affiliation: University of Patras, School of Health Science, Department of Pharmacy, Laboratory of Molecular Biology and Immunology, Greece.
authors.forename: Evangelia Eirini
authors.initials: EE
authors.lastname: Tsermpini
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Laboratory for International Alliance on Genomic Research, Yokohama, Japan; Genomic Medicine Institute, Geisinger Health System, Danville, PA, USA.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, University of Cagliari, Cagliari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Niola
authors.affiliation: Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.affiliation: Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ardau
authors.affiliation: Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bocchetta
authors.affiliation: University of Patras, School of Health Science, Department of Pharmacy, Laboratory of Molecular Biology and Immunology, Greece.
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, University of Cagliari, Cagliari, Italy; Unit of Clinical Pharmacology of the University Hospital of Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, University of Cagliari, Cagliari, Italy. Electronic address: severino@unica.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Severino
authors.affiliation: RIKEN Center for Integrative Medical Sciences, Laboratory for International Alliance on Genomic Research, Yokohama, Japan; Genomic Medicine Institute, Geisinger Health System, Danville, PA, USA. Electronic address: mlee2@geisinger.edu.
authors.forename: Ming Ta Michael
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, University of Cagliari, Cagliari, Italy. Electronic address: squassina@unica.it.
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D018020:Lithium Compounds
keywords: Adverse drug reaction; Bipolar disorder; Genetic variation; Glomerular filtration rate; Kidney; Lithium treatment