| Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population: role of serine protease inhibitor Kazal 1type and alcohol. | |
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MedLine Citation:
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PMID: 18680227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To test the hypothesis that calcium sensing receptor (CASR) polymorphisms are associated with chronic pancreatitis (CP), and to determine whether serine protease inhibitor Kazal 1type (SPINK1) N34S or alcohol are necessary co-factors in its etiology. METHODS: Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms (SNPs) in exon 7 (A986S, R990G, and Q1011E). RESULTS: The CASR exon 7 R990G polymorphism was significantly associated with CP (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015). The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption (OR, 3.12; 95% CI, 1.14-9.13; P = 0.018). There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION: Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a significant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption. |
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Authors:
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Venkata Muddana; Janette Lamb; Julia-B Greer; Beth Elinoff; Robert H Hawes; Peter B Cotton; Michelle A Anderson; Randall E Brand; Adam Slivka; David C Whitcomb |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: World journal of gastroenterology : WJG Volume: 14 ISSN: 1007-9327 ISO Abbreviation: World J. Gastroenterol. Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-08-05 Completed Date: 2008-12-18 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 100883448 Medline TA: World J Gastroenterol Country: China |
Other Details:
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Languages: eng Pagination: 4486-91 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh PA 15213, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Alcohol Drinking / adverse effects* Carrier Proteins / genetics* Case-Control Studies Exons / genetics Female Genetic Predisposition to Disease / genetics Humans Male Middle Aged Mutation / genetics Pancreatitis, Chronic / ethnology, genetics* Polymorphism, Single Nucleotide / genetics* Receptors, Calcium-Sensing / genetics* Risk Factors United States |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK061451/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CASR protein, human; 0/Carrier Proteins; 0/Receptors, Calcium-Sensing; 0/SPINK1 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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