Two closely associated nicotinic acetylcholine receptor genes are involved in increased inflammatory response in human peripheral mononuclear cells.

The vagus nerve, the major nerve of the parasympathetic nervous system, can regulate immune responses in both animals and humans by decreasing the production of pro-inflammatory cytokines, such as TNFα, IL-1β and IL-6. This pathway, referred to as the cholinergic anti-inflammatory pathway, mediates its anti-inflammatory actions via the alpha 7 nicotinic acetylcholine receptor (α7nAChR). Indeed, direct stimulation of the α7nAChR can decrease immune activation and decrease disease progression in both acute and chronic animal models.

In an article in The FASEB Journal, researchers from the University of Gothenburg and from The Human Protein Atlas (HPA) have shown that polymorphisms in the CHRFAM7A gene are associated with inflammatory marker hsCRP in healthy individuals. Furthermore, polymorphisms in the CHRNA7 and/or CHRFAM7A genes can alter cytokine levels, both in unstimulated control cells as well as in LPS challenged cells. However, when cells are challenged with LPS the different genotypes respond differently, most profound is an increased inflammatory response in the AG genotype. Thus, this study demonstrates that CHRNA7 and CHRFAM7A genotypes influence the inflammatory response in human immune cells and demonstrates that the partial duplication of the CHRNA7 gene, the CHRFAM7A, may be an important regulator of immune responses in humans.

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