Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis
Article Type
Research Article
Publication Title
PLoS ONE
Abstract
A recent genome-wide association study (GWAS) identified association with variants in Xlinked 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.
DOI
10.1371/journal.pone.0147345
Publication Date
1-1-2016
Recommended Citation
Giri, Anil K.; Midha, Shallu; Banerjee, Priyanka; Agrawal, Ankita; Mehdi, Syed Jafar; Dhingra, Rajan; Kaur, Ismeet; Kumar, G. Ramesh; Lakhotia, Ritika; Ghosh, Saurabh; Das, Kshaunish; Mohindra, Samir; Rana, Surinder; Bhasin, Deepak K.; Bhasin, Deepak K.; Garg, Pramod K.; Bharadwaj, Dwaipayan; Bhatnagar, Shinjini; Tandon, Nikhil; 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; and Bhansali, Anil, "Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis" (2016). Journal Articles. 4148.
https://digitalcommons.isical.ac.in/journal-articles/4148
Comments
Open Access; Gold Open Access