Abstract | AIM: 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 | 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 |
Journal | World journal of gastroenterology
(World J Gastroenterol)
Vol. 14
Issue 28
Pg. 4486-91
(Jul 28 2008)
ISSN: 1007-9327 [Print] United States |
PMID | 18680227
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- CASR protein, human
- Carrier Proteins
- Receptors, Calcium-Sensing
- SPINK1 protein, human
- Trypsin Inhibitor, Kazal Pancreatic
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Topics |
- 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
- Trypsin Inhibitor, Kazal Pancreatic
- United States
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