In Silico Preliminary Association of Ammonia Metabolism Genes GLS , CPS1 , and GLUL with Risk of Alzheimer ’s Disease, Major Depressive Disorder, and Type 2 Diabetes

AbstractAmmonia is a toxic by-product of protein catabolism and is involved in changes in glutamate metabolism. Therefore, ammonia metabolism genes may link a range of diseases involving glutamate signaling such as Alzheimer ’s disease (AD), major depressive disorder (MDD), and type 2 diabetes (T2D). We analyzed data from a National Institute on Aging study with a family-based design to determine if 45 single nucleotide polymorphisms (SNPs) in glutaminase (GLS), carbamoyl phosphate synthetase 1 (CPS1), or glutamate-ammonia ligase (GLUL) genes were associated with AD, MDD, or T2D using PLINK software. HAPLOVIEW software was used to calculate linkage disequilibrium measures for the SNPs. Next, we analyzed the associated variations for potential effects on transcriptional control sites to identify possible functional effects of the SNPs. Of the SNPs that passed the quality control tests, four SNPs in theGLS gene were significantly associated with AD, two SNPs in theGLS gene were associated with T2D, and one SNP in theGLUL gene and three SNPs in theCPS1 gene were associated with MDD before Bonferroni correction. The in silico bioinformatic analysis suggested probable functional roles for six associated SNPs. Glutamate signaling pathways have been implicated in all these diseases, and other studies have detected similar brain pathologies such as cortical thinning in AD, MDD, and T2D. Taken together, these data potentially linkGLS with AD,GLS with T2D, andCPS1 andGLUL with MDD an...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research