Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians
by Srinivasan Pugazhendhi, Kirankumar Baskaran, Srikanth Santhanam, Balakrishnan S. RamakrishnaInflammatory 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.
Publisher URL: http://journals.plos.org/plosone/article
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