Crohn's disease IRGM risk alleles are associated with altered gene expression in human tissues.

Crohn's disease IRGM risk alleles are associated with altered gene expression in human tissues. Am J Physiol Gastrointest Liver Physiol. 2018 Oct 18;: Authors: Ajayi T, Innes CL, Grimm SA, Rai P, Finethy R, Coers J, Wang X, Bell DA, McGrath JA, Schurman SH, Fessler MB Abstract Crohn's disease (CD) is a chronic inflammatory gastrointestinal disorder. Genetic association studies have implicated dysregulated autophagy in CD. Among risk loci identified are a promoter single nucleotide polymorphism (SNP)(rs13361189) and two intragenic SNPs (rs9637876, rs10065172) in immunity-related GTPase family M ( IRGM), a gene that encodes a protein of the autophagy initiation complex. All three SNPs have been proposed to modify IRGM expression, but reports have been divergent and largely derived from cell lines. Here, analyzing RNA-Sequencing data of human tissues from the Genotype-Tissue Expression Project, we found that rs13361189 minor allele carriers had reduced IRGM expression in whole blood and terminal ileum, and upregulation in ileum of ZNF300P1, a locus adjacent to IRGM on chromosome 5q33.1 that encodes a long noncoding RNA. Whole blood and ileum from minor allele carriers had altered expression of multiple additional genes that have previously been linked to colitis and/or autophagy. Notable among these was an increase in ileum of LTF (lactoferrin), an established fecal inflammatory biomarker of CD, and in whole blood of TNF, a key cytokine...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research