Characterizing Six Genotypes of the Cholinergic Receptor Nicotinic Alpha 7 Genes CHRNA7 and Duplication CHRFAM7A with TaqMan, Poster 42

Patients with Rheumatoid Arthritis (RA) are characterized by an underactive inflammatory reflex, which can be restored through vagal nerve stimulation (VNS). CHRNA7 is the gene responsible for the alpha-7 nicotnic ACh... [ view full abstract ]

Patients with Rheumatoid Arthritis (RA) are characterized by an underactive inflammatory reflex, which can be restored through vagal nerve stimulation (VNS). CHRNA7 is the gene responsible for the alpha-7 nicotnic ACh receptor (nAChR), a mediator of the inflammatory reflex. A duplication of the gene exists, CHRFAM7A, which can have a 2 base pair deletion, causing a frameshift. The translated duplicated gene forms compromised alpha-7 nAChRs, which may lead to a change in the functional efficacy of VNS. We hypothesized that we could quantitatively determine the different genotypes of individuals through ratios of wild-type to mutant DNA levels. We genotyped a set of individuals using a copy number assay and a custom-designed TaqMan assay in order to characterize both the presence/absence of the 2 base pair deletion and the number of collective CHRNA7 and CHRFAM7A copies. Using established genotypic frequencies, we were able to verify the accuracy of our assays, allowing for future study of phenotypic differences of response to VNS amongst RA patients.