TheATG16L1Gene Variants rs2241879 and rs2241880 (T300A) Are Strongly Associated With Susceptibility to Crohn's Disease in the German Population

Abstract

ATG16L1 is a CD susceptibility gene without epistatic interaction with other CD susceptibility genes and is not upregulated in intestinal inflammation.

Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach

“…Interestingly, in a very recent study McCarroll et al 56 have shown that the causal variant responsible for IRGM Figure 1 Pooled data for the ATG16L1 rs2241880 susceptibility allele frequency (SAF). (a) Pooled data of Australian, 39 Belgian, 16 British, 14,21,23,25 Canadian, 31 Dutch, 28 German, 14,29,30 Italian, 27,33 Hungarian, 34 Japanese, 22 New Zealander, 26 North American 15,24 and Spanish cohorts for Crohn's disease (CD). (b) Pooled data of Australian, 39 British, 21,23,37 Canadian, 31 Dutch, 28 German, 14,29,30 Italian, 33 Hungarian, 34 New Zealander, 26,39 North American 15 and Spanish cohorts for ulcerative colitis (UC).…”

“…[14][15][16][21][22][23][24][25][26][27][28][29][30][31][32][33][34]38,39 Funnel plots and Egger tests were performed to analyse the publication bias of the meta-analysis. No statistically significant values were observed in CD studies (P ¼ 0.6) or UC studies (P ¼ 0.4), with symmetric funnel plots for both studies (Supplementary Figure 1).…”

“…[14][15][16] A large number of subsequent association studies have replicated the strong association of this gene with CD. [21][22][23][24][25][26][27][28][29][30][31][32][33][34] IRGM (immunity-related guanosine triphosphatase, the human homologue of mouse Irgm/Lrg47) encodes a GTP-binding protein that induces autophagy and plays an important role in innate immunity against intracellular pathogens. 35,36 Association of two immediately flanking IRGM gene polymorphisms (rs13361189 and rs4958847) with CD has recently been reported.…”

ATG16L1: A multifunctional susceptibility factor in Crohn disease

“…35 In particular, 9 genetic variants of ATG16L1 (rs13412102, rs12471449, rs6431660, rs1441090, rs2289472, rs2241880, rs2241879, rs3792106, and rs4663396) are associated with Crohn disease, although only rs6431660 is weakly associated with UC. 52 The variant rs3792106 is linked to sex differences due to a correlation between this gene variant and the fact that women with Crohn disease are more prone to surgical Figure 1. Schematic stages of the autophagic pathway.…”

“…Numerous GWAS reports have identified several SNPs that regulate or communicate with the autophagic pathways and represent risk factors for Crohn disease. 7,[52][53][54][55][56][57][58] For instance, the SNPs in NOD2 are the most prominent risk-associated SNPs and can lead to early disease onset and a more complicated clinical course of Crohn disease, including fibrostenosis and fistulization. 11 These genetic variations also exhibit a marked reduction in bacterial autophagy due to the fact that NOD2 recruits ATG16L1 to the site of bacterial entry, 10 as described in more detail below.…”