Polymorphisms in alpha 7 nicotinic acetylcholine receptor gene, CHRNA7, and its partially duplicated gene, CHRFAM7A, associate with increased inflammatory response in human peripheral mononuclear cells. Issue 5 (28th March 2022)

• Record Type: Journal Article
• Authors: Pattanaik, Bagmi; Hammarlund, Maria; Mjörnstedt, Filip; Ulleryd, Marcus A.; Zhong, Wen; Uhlén, Mathias; Gummesson, Anders; Bergström, Göran; Johansson, Maria E.
• Is Part Of: FASEB journal. Volume 36:Issue 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-28
• Subjects: alpha 7 nicotinic acetylcholine receptor -- CHRFAM7A -- CHRNA7 -- immune response -- inflammation -- polymorphisms -- α7nAChR; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202101898R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: The vagus nerve can, via the alpha 7 nicotinic acetylcholine receptor (α7nAChR), regulate inflammation. The gene coding for the α7nAChR, CHRNA7, can be partially duplicated, that is, CHRFAM7A, which is reported to impair the anti‐inflammatory effect mediated via the α7nAChR. Several single nucleotide polymorphisms (SNPs) have been described in both CHRNA7 and CHRFAM7A, however, the functional role of these SNPs for immune responses remains to be investigated. In the current study, we set out to investigate whether genetic variants of CHRNA7 and CHRFAM7A can influence immune responses. By investigating data available from the Swedish SciLifeLab SCAPIS Wellness Profiling (S3WP) study, in combination with droplet digital PCR and freshly isolated PBMCs from the S3WP participants, challenged with lipopolysaccharide (LPS), we show that CHRNA7 and CHRFAM7A are expressed in human PBMCs, with approximately four times higher expression of CHRFAM7A compared with CHRNA7 . One SNP in CHRFAM7A, rs34007223, is positively associated with hsCRP in healthy individuals. Furthermore, gene ontology (GO)‐terms analysis of plasma proteins associated with gene expression of CHRNA7 and CHRFAM7A demonstrated an involvement for these genes in immune responses. This was further supported by in vitro data showing that several SNPs in both CHRNA7 and CHRFAM7A are significantly associated with cytokine response. In conclusion, genetic variants of CHRNA7 and CHRFAM7A alters cytokine responses. Furthermore, given that CHRFAM7A SNP rs34007223 is associated with inflammatory marker hsCRP in healthy individuals suggests that CHRFAM7A may have a more pronounced role in regulating inflammatory processes in humans than previously been recognized.