Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
PloS one - 11(2016), 1 vom: 23., Seite e0147345 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Giri, Anil K [VerfasserIn] |
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| Links: |
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| Themen: |
CLDN2 protein, human |
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| Anmerkungen: |
Date Completed 06.07.2016 Date Revised 17.03.2022 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0147345 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM256932115 |
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| 245 | 1 | 0 | |a Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a CLDN2 protein, human |2 NLM | |
| 650 | 7 | |a Claudins |2 NLM | |
| 650 | 7 | |a MORC4 protein, human |2 NLM | |
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| 700 | 1 | |a Agrawal, Ankita |e verfasserin |4 aut | |
| 700 | 1 | |a Mehdi, Syed Jafar |e verfasserin |4 aut | |
| 700 | 1 | |a Dhingra, Rajan |e verfasserin |4 aut | |
| 700 | 1 | |a Kaur, Ismeet |e verfasserin |4 aut | |
| 700 | 1 | |a G, Ramesh Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Lakhotia, Ritika |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Saurabh |e verfasserin |4 aut | |
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| 700 | 1 | |a Garg, Pramod K |e verfasserin |4 aut | |
| 700 | 1 | |a Bharadwaj, Dwaipayan |e verfasserin |4 aut | |
| 700 | 0 | |a INDIPAN and INDICO Consortium |e verfasserin |4 aut | |
| 700 | 1 | |a Mohan, Viswanathan |e investigator |4 oth | |
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| 700 | 1 | |a Tabassum, Rubina |e investigator |4 oth | |
| 700 | 1 | |a Mahajan, Anubha |e investigator |4 oth | |
| 700 | 1 | |a Dwivedi, Prakash |e investigator |4 oth | |
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| 700 | 1 | |a Venkatesan, Radha |e investigator |4 oth | |
| 700 | 1 | |a Chidambaram, M |e investigator |4 oth | |
| 700 | 1 | |a Prabhakaran, D |e investigator |4 oth | |
| 700 | 1 | |a Reddy, K S |e investigator |4 oth | |
| 700 | 1 | |a Banerjee, Monisha |e investigator |4 oth | |
| 700 | 1 | |a Saxena, Madhukar |e investigator |4 oth | |
| 700 | 1 | |a Mathur, Sandeep |e investigator |4 oth | |
| 700 | 1 | |a Bhansali, Anil |e investigator |4 oth | |
| 700 | 1 | |a Shah, Viral |e investigator |4 oth | |
| 700 | 1 | |a Madhu, S V |e investigator |4 oth | |
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| 700 | 1 | |a Venkatesh, Pradeep |e investigator |4 oth | |
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