 |
 |
A variant in a gene that converts vitamin B6 to a cofactor for dopamine synthesis is implicated in some cases of Parkinson's disease, according to a new study. The study used gene expression profiling (i.e., determining changes in messenger RNA production) to identify candidate genes, and then determined whether variants in those genes were associated with disease, a process called "genomic convergence." The value of such a study design is that it can detect associations weaker than those currently found through genome-wide association studies. The authors performed whole-genome expression profiling in 100 individual substantia nigra cells from a single individual from a brain bank PD case. After Bonferroni correction and confirmation by real-time expression analysis, several genes were identified as significantly altered between PD and control cells. Variants of one, PDXK (pyridoxal kinase), were found to be associated with PD in three European cohorts. "PDXK catalyzes the conversion of vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine) to pyridoxal 5'-phosphate (PLP)," the authors state. PLP is thought to be a cofactor in multiple reactions, including the biosynthesis of dopamine by dopa decarboxylase. "Upregulation of PDXK in dopaminergic neurons may be explained by an adaptive mechanism to increase dopamine metabolism in the remaining funcitonal dopaminergic neurons of the SNc or to levodopa therapy." The authors speculate that the polymorphism associated with PD may influence enzyme amount or activity. Dietary vitamin B6 has previously been linked to a reduced risk of PD in smokers. Single-cell expression profiling ofdopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene M Elstner, CM Morris, K Heim, et al. Ann Neurol 2009;66:792-798 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn