The role of M1 to M2 macrophage polarization in the etiology of idiopathic gastroparesis: GWAS perspective

Abstract Gastroparesis is a serious medical condition characterized by delayed gastric emptying. An innate immune dysregulation and injury to the interstitial cells of Cajal other components enteric nervous system likely central pathogenesis gastroparesis. We have done GWAS comparing idiopathic diabetic cases with controls as well contrasting versus cases. report novel genetic association SLC15A4 locus This signal driven multiple variants top missense variant SLC15A4:NM145648:exon2:c.T716C:p.V239A, rs33990080. Altogether, among EUR cohort we 69 carriers out 214 165 896 (MAF: 0.18; MAF: 0.09) OR: 1.9 (p-value logistic model 10^−6). The significant effect persists when are compared MAF (0.10) comparable that population (0.09). Solute carrier family 15 (SLC15) A4 lysosome-resident amino acid/oligopeptide transporter preferentially expressed in cells. It required for TLR7/9-dependent type I interferon production plays critical role lupus colitis. was shown mediate M1-prone metabolic shifts macrophages guards from stress. Previous reports anti-inflammatory M2 switched pro-inflammatory M1 macrophages, GE evident animal models. Current findings suggest mechanism directly connected macrophage polarization may be implicated subset gastroparesis patients.