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Exploring Lithium Impact on Glomerular Function in Bipolar Patients Through Pharmacogenomics

Published online by Cambridge University Press:  23 March 2020

E.E. Tsermpini ,
Y. Zhang ,
P. Niola ,
C. Chillotti ,
R. Ardau ,
G. Severino ,
A. Bocchetta ,
G.P. Patrinos ,
M.T.M. Lee  and
A. Squassina
E.E. Tsermpini
Affiliation:
University of Patras, School of Health Science, Department of Pharmacy, Laboratory of Molecular Biology and Immunology, Patras, Greece
Y. Zhang
Affiliation:
RIKEN Center for Integrative Medical Sciences, Laboratory for International Alliance on Genomic Research, Yokohama, Japan
P. Niola
Affiliation:
University of Cagliari, Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, Cagliari, Italy
C. Chillotti
Affiliation:
University Hospital of Cagliari, Unit of Clinical Pharmacology, Cagliari, Italy
R. Ardau
Affiliation:
University Hospital of Cagliari, Unit of Clinical Pharmacology, Cagliari, Italy
G. Severino
Affiliation:
University of Cagliari, Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, Cagliari, Italy
A. Bocchetta
Affiliation:
University Hospital of Cagliari, Unit of Clinical Pharmacology, Cagliari, Italy
G.P. Patrinos
Affiliation:
University of Patras, School of Health Science, Department of Pharmacy, Laboratory of Molecular Biology and Immunology, Patras, Greece
M.T.M. Lee
Affiliation:
RIKEN Center for Integrative Medical Sciences, Laboratory for International Alliance on Genomic Research, Yokohama, Japan
A. Squassina
Affiliation:
University of Cagliari, Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, School of Medicine, Cagliari, Italy

Abstract

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Introduction

Bipolar disorder (BD) is characterized by unusual shifts in mood and energy and affects 1 to 3% of the general population. Lithium (Li) can prevent patients from depression and mania, as well as reduce the risk of suicide. Unfortunately, a high rate of patients do not respond positively to Li treatment. In line with various studies, Li treatment is also associated with potentially severe adverse reactions, including renal dysfunctions. Specifically, it has been reported that Li may induce reduction of glomerular filtration rate (GFR) in long-term treated BD patients.

Aims

The aim of our study was to evaluate the contribution of genetic variants in Li-induced reduction of the estimated GFR (eGFR) in bipolar patients, under long term Li therapy.

Objectives

We screened the literature to identify genes previously shown to be associated with kidney function or Li mechanism of action and genotyped tag SNPs covering these genes.

Methods

The sample comprised 70 Sardinian bipolar patients genotyped for 46 SNPs, located in 33 genes, with Invader assay and Sanger sequencing.

Results

Our results showed that a SNP (rs378448) located in Acid Sensing Ion Channel Neurona-1 (ACCN1) gene, significantly interacted with years of Li treatment in reducing eGFR (F = 4.166, P = 0.046).

Conclusions

Our preliminary findings suggest that ACCN1 (ASIC2) gene could be involved in modulating the susceptibility of BD patients to develop renal dysfunctions induced by chronic Li treatment.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
Oral communications: Rehabilitation and psychoeducation and schizophrenia and other psychotic disorders
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. S102 - S103
Copyright
Copyright © European Psychiatric Association 2017
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