Pugazhendhi Srinivasan, Baskaran Kirankumar, Santhanam Srikanth, Ramakrishna Balakrishnan S
Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India.
PLoS One. 2017 May 19;12(5):e0178291. doi: 10.1371/journal.pone.0178291. eCollection 2017.
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.
炎症性肠病（IBD）具有多基因遗传特征。自噬相关基因的缺陷被认为在不同人群中表现出遗传异质性。我们评估了自噬相关16样1（ATG16L1）基因中的几个单核苷酸多态性（SNP）与印度人IBD的关联。使用从234例克罗恩病（CD）患者、249例溃疡性结肠炎（UC）患者和393名健康对照者的外周血中提取的DNA，对ATG16L1基因的10个不同SNP进行基因分型。使用Sequenom MassArray平台对SNP rs2241880、rs4663396、rs3792106、rs10210302、rs3792109、rs2241877、rs6737398、rs11682898、rs4663402和rs4663421进行基因分型。使用PLINK进行关联分析和成对连锁不平衡（LD）值计算。使用Haploview进行单倍型分析。所有SNP在病例组和对照组中均处于哈迪-温伯格平衡。rs6737398处的G等位基因与CD和UC均表现出保护性关联。rs4663402处的T等位基因和rs4663421处的C等位基因与CD和UC呈正相关。rs2241877处的T等位基因仅与UC表现出保护性关联。rs4663402处的AA基因型和rs4663421处的GG基因型与CD和UC均呈保护性关联。单倍型分析显示，所有紧密连锁不平衡（D' = 0.76 - 1.0）的SNP并组成一个单倍型块。单倍型D与IBD呈正相关（CD的P = 5.8 x 10 - 6，UC的P = 0.002）。ATG16L1基因中的SNP与印度患者的IBD相关。其与个体患者管理的相关性需要进一步研究。
