TY - JOUR
T1 - Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis
AU - INDICO Consortium
AU - Giri, Anil K.
AU - Midha, Shallu
AU - Banerjee, Priyanka
AU - Agrawal, Ankita
AU - Mehdi, Syed Jafar
AU - Dhingra, Rajan
AU - Kaur, Ismeet
AU - Kumar, G. Ramesh
AU - Lakhotia, Ritika
AU - Ghosh, Saurabh
AU - Das, Kshaunish
AU - Mohindra, Samir
AU - Rana, Surinder
AU - Bhasin, Deepak K.
AU - Garg, Pramod K.
AU - Bharadwaj, Dwaipayan
AU - Bhatnagar, Shinjini
AU - Bhasin, Deepak Kumar
AU - Tandon, Nikhil
AU - Mohan, Viswanathan
AU - Sharma, Abhay
AU - Tabassum, Rubina
AU - Mahajan, Anubha
AU - Dwivedi, Om Prakash
AU - Ramakrishnan, Lakshmi
AU - Venkatesan, Radha
AU - Chidambaram, M.
AU - Prabhakaran, D.
AU - Reddy, K. S.
AU - Banerjee, Monisha
AU - Saxena, Madhukar
AU - Mathur, Sandeep
AU - Bhansali, Anil
AU - Shah, Viral
AU - Madhu, S. V.
AU - Marwah, R. K.
AU - Venkatesh, Pradeep
AU - Aggarwal, S. K.
AU - Gupta, Shantanu Sen
AU - Chavali, Sreenivas
AU - Sharma, Amitabh
AU - Basu, Analabha
AU - Bandesh, Khushdeep
AU - Chakraborty, Shraddha
AU - Kauser, Yasmeen
AU - Abitha, B.
AU - Undru, Aditya
AU - Rajashekar, Donaka
AU - Parekatt, Vaisak
AU - Roy, Suki
N1 - Publisher Copyright:
© 2016 Giri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84958818440&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0147345
DO - 10.1371/journal.pone.0147345
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C2 - 26820620
AN - SCOPUS:84958818440
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0147345
ER -