Exploring lithium impact on glomerular function in bipolar patients through pharmacogenomics

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.