Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians

Abstract

Inflammatory bowel disease (IBD) is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs) in the autophagy related 16 like 1 (ATG16L1) gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn’s disease (CD), 249 patients with ulcerative colitis (UC) and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD) values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D’ = 0.76–1.0) and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10−6 for CD and 0.002 for UC). SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

MiRNAs and inflammatory bowel disease: An interesting new story

“…Studies have shown that some of the effective genes in autophagy, including ATG16L1 and IRGM, are associated with IBD, especially Crohn's disease (Kabat et al, 2016;X. C. Lu et al, 2013;Moon et al, 2012;Nguyen et al, 2014;Nunes et al, 2014;Pugazhendhi, Baskaran, Santhanam, & Ramakrishna, 2017). ATG16L1, as an adaptor protein, is constitute an ATG5-binding region and coiled-coil domain (CCD; for self-dimerization), in N-and amino terminal, respectively (Mizushima et al, 2003).…”

“…Autophagy is a process that greatly helps in saving cellular energy by eliminating unnecessary components; this condition is more important in certain conditions, such as those in which food shortages exist or while dealing with pathogens (Nunes et al, ). Studies have shown that some of the effective genes in autophagy, including ATG16L1 and IRGM, are associated with IBD, especially Crohn's disease (Kabat et al, ; X. C. Lu et al, ; Moon et al, ; Nguyen et al, ; Nunes et al, ; Pugazhendhi, Baskaran, Santhanam, & Ramakrishna, ). ATG16L1, as an adaptor protein, is constitute an ATG5‐binding region and coiled‐coil domain (CCD; for self‐dimerization), in N‐ and amino terminal, respectively (Mizushima et al, ).…”

Associations between ATG16L1 gene polymorphism and antineutrophil cytoplasmic antibody‐associated vasculitis in the Chinese Guangxi population: A case–control study

“… 26 In addition, ATG16L1 rs2241880 polymorphism is associated with rheumatoid arthritis in China. 27 Pugazhendhi 21 confirmed that the allele and genotype frequencies of the ATG16L1 mutant rs4663402 are associated with Crohn's disease and ulcerative colitis in India. Similarly, Glas et al 28 indicated that a protective association between rs4663396 and Crohn's disease has also been confirmed in Germany.…”

Newly Diagnosed Crohn’s Disease Patients in India and Israel Display Distinct Presentations and Serological Markers: Insights from Prospective Cohorts

“…Some of these antibodies were specifically associated with CD diagnosis and complications in several studies [ 13 , 14 , 36 ]. Antiglycan serologic responses in Indian patients with CD [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] and non-Indian Asian cohorts [ 38 , 39 ] were scarcely reported. Interestingly, despite a comparable overall rate of seropositivity, differences between the cohorts were noticed.…”

“…Quality and quantity were tested using a NanoDrop One spectrophotometer (Thermo Scientific, Waltham, MA, USA). To explore possible genetic biomarkers, we genotyped 20 CD-associated single-nucleotide polymorphisms (SNPs) that were reported in either Western ( n = 13) or Indian ( n = 7) cohorts in association with CD diagnosis [ 19 , 20 , 21 ] and course [ 22 , 23 ] (listed in Supplementary Table S1 ). These included polymorphisms in protein binding domain 2 ( NOD2 ) [ 24 ] and the genes regulating the autophagic response to invading pathogens (autophagy pathway-related 16 like 1 ( ATG16L1 ) and immunity-related GTPase 1 ( IRGM )) [ 25 ].…”