title: Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis.
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.
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.|Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Giri
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Shallu
authors.initials: S
authors.lastname: Midha
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Syed Jafar
authors.initials: SJ
authors.lastname: Mehdi
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Dhingra
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Ismeet
authors.initials: I
authors.lastname: Kaur
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Ramesh Kumar
authors.initials: RK
authors.lastname: G
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
authors.forename: Ritika
authors.initials: R
authors.lastname: Lakhotia
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata, India.
authors.forename: Kshaunish
authors.initials: K
authors.lastname: Das
authors.affiliation: Department of Gastroenterology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Samir
authors.initials: S
authors.lastname: Mohindra
authors.affiliation: Department of Gastroenterology, Post-graduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Surinder
authors.initials: S
authors.lastname: Rana
authors.affiliation: Department of Gastroenterology, Post-graduate Institute of Medical Education & Research, Chandigarh, India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Bhasin
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Garg
authors.affiliation: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.|Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi, India.
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D057167:Claudins / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C491875:CLDN2 protein, human; D057167:Claudins; C523050:MORC4 protein, human; D009687:Nuclear Proteins
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