Pharmacogenetics of lithium effects on glomerular function in bipolar disorder patients under chronic lithium...

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.