Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

Giri, Anil K. ; Midha, Shallu ; Banerjee, Priyanka ; Agrawal, Ankita ; Mehdi, Syed Jafar ; Dhingra, Rajan ; Kaur, Ismeet ; G., Ramesh Kumar ; Lakhotia, Ritika ; Ghosh, Saurabh ; Das, Kshaunish ; Mohindra, Samir ; Rana, Surinder ; Bhasin, Deepak K. ; Garg, Pramod K. ; Bharadwaj, Dwaipayan ; Bhatnagar, Shinjini ; Mohan, Viswanathan ; Sharma, Abhay ; Tabassum, Rubina ; Mahajan, Anubha ; Dwivedi, Om Prakash ; Ramakrishnan, Lakshmi ; Venkatesan, Radha ; Chidambaram, M. ; Prabhakaran, D. ; Reddy, K. S. ; Banerjee, Monisha ; Saxena, Madhukar ; Mathur, Sandeep ; Bhansali, Anil ; Shah, Viral ; Madhu, S. V. ; Marwah, R. K. ; Venkatesh, Pradeep ; Aggarwal, S. K. ; Sen Gupta, Shantanu ; Chavali, Sreenivas ; Sharma, Amitabh ; Basu, Analabha ; Bandesh, Khushdeep ; Chakraborty, Shraddha ; Kauser, Yasmeen ; Abitha, B. ; Undru, Aditya ; Rajashekar, Donaka ; Parekatt, Vaisak ; Roy, Suki ; Das, Debajyoti ; Ravindran, Aarthi ; Singh, Anjali ; Prasad, Gauri ; Jha, Punam ; Tandon, Nikhil (2016) Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis PLoS One, 11 (1). Article ID e0147345. ISSN 1932-6203

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Official URL: http://journals.plos.org/plosone/article?id=10.137...

Related URL: http://dx.doi.org/10.1371/journal.pone.0147345

Abstract

A recent Genome-wide Association Study (GWAS) identified association with variants in X-linked CLDN2 and MORC4 and PRSS1-PRSS2 loci with Chronic Pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

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ID Code:106895
Deposited On:26 Jun 2017 12:54
Last Modified:26 Jun 2017 12:54

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