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Table of Contents
Vol. 8, No. 4-5, 2008
Issue release date: October 2008
Section title: Original Paper
Free Access
Pancreatology 2008;8:520–531
(DOI:10.1159/000152001)

Multicenter Approach to Recurrent Acute and Chronic Pancreatitis in the United States: The North American Pancreatitis Study 2 (NAPS2)

Whitcomb D.C.a, b · Yadav D.a · Adam S.a · Hawes R.H.c · Brand R.E.d · Anderson M.A.e · Money M.E.f · Banks P.A.g · Bishop M.D.h · Baillie J.i · Sherman S.j · DiSario J.k · Burton F.R.l · Gardner T.B.m · Amann S.T.n · Gelrud A.o · Lo S.L.p · DeMeo M.T.q · Steinberg W.M.r · Kochman M.L.s · Etemad B.t · Forsmark C.E.u · Elinoff B.a · Greer J.B.a · O’Connell M.a · Lamb J.a · Barmada M.M.b
Departments of aMedicine and bHuman Genetics, University of Pittsburgh, Pittsburgh, Pa.; cDigestive Disease Center, Medical University of South Carolina, Charleston, S.C.; dDepartment of Medicine, Evanston Northwestern Healthcare, Evanston, Ill.; eUniversity of Michigan, Ann Arbor, Mich.; fWashington County Hospital, Hagerstown, Md.; gDivision of Gastroenterology, Brigham and Women’s Hospital, Boston, Mass.; hDivision of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Fla.; iDepartment of Medicine, Duke University Medical Center, Durham, N.C.; jDepartment of Medicine, Indiana University Medical Center, Indianapolis, Ind.; kDepartment of Medicine, University of Utah Health Science Center, Salt Lake City, Utah; lDepartment of Internal Medicine, St. Louis University School of Medicine, St. Louis, Mo.; mDartmouth-Hitchcock Medical Center, Hanover, N.H.; nNorth Mississippi Medical Center, Tupelo, Miss.; oDepartment of Internal Medicine, University of Cincinnati, Cincinnati, Ohio; pDepartment of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles, Calif.; qDepartment of Medicine, Rush University Medical Center, Chicago, Ill.; rWashington Hospital Center, Washington, D.C.; sDepartment of Medicine, University of Pennsylvania, Philadelphia, Pa.; tDepartment of Gastroenterology and Hepatology, Ochsner Medical Center, New Orleans, La., and uDepartment of Medicine, University of Florida, Gainesville, Fla., USA
email Corresponding Author

Abstract

Background: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are complex syndromes associated with numerous etiologies, clinical variables and complications. We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP. Methods: Between August 2000 and September 2006, a consortium of 20 expert academic and private sites prospectively ascertained 1,000 human subjects with RAP or CP, plus 695 controls (spouse, family, friend or unrelated). Standardized questionnaires were completed by both the physicians and study subjects and blood was drawn for genomic DNA and biomarker studies. All data were double-entered into a database and systematically reviewed to minimize errors and include missing data. Results: A total of 1,000 subjects (460 RAP, 540 CP) and 695 controls who completed consent forms and questionnaires and donated blood samples comprised the final dataset. Data were organized according to diagnosis, supporting documentation, etiological classification, clinical signs and symptoms (including pain patterns and duration, and quality of life), past medical history, family history, environmental exposures (including alcohol and tobacco use), medication use and therapeutic interventions. Upon achieving the target enrollment, data were organized and classified to facilitate future analysis. The approaches, rationale and datasets are described, along with final demographic results. Conclusion: The NAPS2 consortium has successfully completed a prospective ascertainment of 1,000 subjects with RAP and CP from the USA. These data will be useful in elucidating the environmental, metabolic and genetic conditions, and to investigate the complex interactions that underlie RAP and CP.

© 2008 S. Karger AG, Basel and IAP


  

Key Words

  • North American Pancreatitis Study 2
  • NAPS2 United States
  • Recurrent acute pancreatitis
  • Chronic pancreatitis

References

  1. Somogyi L, Martin SP, Ulrich CD: Recurrent acute pancreatitis. Curr Treat Options Gastroenterol 2001;4:361–368.
  2. Steer ML, Waxman I, Freedman S: Chronic pancreatitis. N Engl J Med 1995;332:1482–1490.
  3. Etemad B, Whitcomb DC: Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology 2001;120:682–707.
  4. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, et al: Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996;14:141–145.
  5. Whitcomb DC: Hereditary pancreatitis: new insights into acute and chronic pancreatitis. Gut 1999;45:317–322.
  6. Audrezet MP, Chen JM, Le Marechal C, Ruszniewski P, Robaszkiewicz M, Raguenes O, et al: Determination of the relative contribution of three genes – the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene – to the etiology of idiopathic chronic pancreatitis. Eur J Hum Genet 2002;10:100–106.
  7. Bernardino AL, Guarita DR, Mott CB, Pedroso MR, Machado MC, Laudanna AA, et al: CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients. JOP 2003;4:169–177.

    External Resources

  8. Ockenga J, Stuhrmann M, Ballmann M, Teich N, Keim V, Dork T, et al: Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are associated with recurrent or chronic idiopathic pancreatitis. Am J Gastroenterol 2000;95:2061–2067.
  9. Applebaum-Shapiro SE, Finch R, Pfützer RH, Hepp LA, Gates L, Amann S, et al: Hereditary pancreatitis in North America: The Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study. Pancreatology 2001;1:439–443.
  10. Whitcomb DC: Conference report: Pittsburgh Pancreasfest 2005. Pancreatology 2005;6:138–140.
  11. Sarner M, Cotton PB: Classification of pancreatitis. Gut 1984;25:756–759.
  12. Bradley KA, Boyd-Wickizer J, Powell SH, Burman ML: Alcohol screening questionnaires in women: a critical review. JAMA 1998;280:166–171.
  13. National Center for Health Statistics, Health, United States, 2006; with Chartbook on Trends in the Health of Americans. Hyattesville, 2006.
  14. Warshaw A, Banks PA, Femandez-del Castillo C: AGA technical review: treatment of pain in chronic pancreatitis. Gastroenterology 1998;115:765–776.
  15. Ammann RW, Muellhaupt B, Group ZPS: The natural history of pain in alcoholic chronic pancreatitis. Gastroenterology 1999;116:1132–1140.
  16. Bloechle C, Izbicki JR, Knoefel WT, Kuechler T, Broelsch CE: Quality of life in chronic pancreatitis – results after duodenum-preserving resection of the head of the pancreas. Pancreas 1995;11:77–85.
  17. Whitcomb DC, Barmada MM: A systems biology approach to genetic studies of pancreatitis and other complex diseases. Cell Mol Life Sci 2007;64:1763–1777.
  18. Whitcomb DC, Aoun E, Vodovotz Y, Clermont G, Barmada MM: Evaluating disorders with a complex genetics basis: the future role of meta-analysis and systems biology. Dig Dis Sci 2005;50:2195–2202.
  19. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG: Replication validity of genetic association studies. Nat Genet 2001;29:306–309.
  20. Ioannidis JP, Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG: Genetic associations in large versus small studies: an empirical assessment. Lancet 2003;361:567–571.
  21. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006;314:1461–1463.
  22. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al: Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 2007;39:596–604.
  23. Whitcomb DC: Mechanisms of disease: advances in understanding the mechanisms leading to chronic pancreatitis. Nat Clin Pract Gastroenterol Hepatol 2004;1:46–52.
  24. Manolio TA, Bailey-Wilson JE, Collins FS: Genes, environment and the value of prospective cohort studies. Nat Rev Genet 2006;7:812–820.
  25. Whitcomb DC: Value of genetic testing in management of pancreatitis. Gut 2004;53:1710–1717.
  26. Schneider A, Pfützer RH, Barmada MM, Slivka A, Martin J, Whitcomb DC: Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis – a preliminary report from the United States. Dig Dis Sci 2003;48:1110–1115.
  27. Schneider A, Pogue-Geile K, Barmada MM, Myers-Fong E, Thompson BS, Whitcomb DC: Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-α) promoter region or the TNF receptor 1 (TNFR1) gene. Genet Med 2003;5:120–125.
  28. Oruc N, Lamb J, Kutlu OC, Barmada MM, Money ME, Slivka A, et al: The functional angiotensin-converting enzyme gene I/D polymorphism does not alter susceptibility to chronic pancreatitis. JOP 2004;5:457–463.

    External Resources

  29. Schneider A, Barmada MM, Slivka A, Martin JA, Whitcomb DC: Analysis of tumor necrosis factor-α, transforming growth factor-β, interleukin-10, and interferon-γ polymorphisms in patients with alcoholic chronic pancreatitis. Alcohol 2004;32:19–24.
  30. Schneider A, Togel S, Barmada MM, Whitcomb DC: Genetic analysis of the glutathione S-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis. J Gastroenterol 2004;39:783–787.
  31. Schneider A, Lamb J, Barmada MM, Cuneo A, Money ME, Whitcomb DC: Keratin 8 mutations are not associated with familial, sporadic and alcoholic pancreatitis in a population from the United States. Pancreatology 2005;6:103–108.
  32. Schneider A, Lawrence EC, Barmada MM, Norris JM, Hamman RF, Marshall JA, et al: The SPINK1 N34S mutation is not associated with type 2 diabetes mellitus in a population of the USA. Diabet Med 2005;22:744–748.
  33. Zeh HJ, Winikoff S, Landsittel DP, Gorelik E, Marrangoni AM, Velikokhatnaya L, et al: Multianalyte profiling of serum cytokines for detection of pancreatic cancer. Cancer Biomark 2005;1:259–269.
  34. Sass DA, Papachristou GI, Lamb J, Barmada MM, Brand RE, Money ME, et al: The MCP-1 -2518 A/G polymorphism is not a susceptibility factor for chronic pancreatitis. Pancreatology 2006;6:297–300.
  35. Bhat YM, Papachristou GI, Park JS, Lamb J, Slivka A, Whitcomb DC: Functional polymorphisms of the GSTT-1 gene do not predict the severity of acute pancreatitis in the United States. Pancreatology 2007;7:180–186.

  

Author Contacts

David C. Whitcomb, MD, PhD
UPMC Presbyterian, M2 C-Wing
200 Lothrop Street, Pittsburgh, PA 15213 (USA)
Tel. +1 412 648 9604, Fax +1 412 383 7236
E-Mail whitcomb@pitt.edu

  

Article Information

Received: November 5, 2007
Accepted after revision: February 21, 2008
Published online: September 3, 2008
Number of Print Pages : 12
Number of Figures : 0, Number of Tables : 7, Number of References : 35

  

Publication Details

Pancreatology

Vol. 8, No. 4-5, Year 2008 (Cover Date: October 2008)

Journal Editor: Urrutia R. (Rochester, Minn.)
ISSN: 1424–3903 (Print), eISSN: 1424–3911 (Online)

For additional information: http://www.karger.com/PAN


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are complex syndromes associated with numerous etiologies, clinical variables and complications. We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP. Methods: Between August 2000 and September 2006, a consortium of 20 expert academic and private sites prospectively ascertained 1,000 human subjects with RAP or CP, plus 695 controls (spouse, family, friend or unrelated). Standardized questionnaires were completed by both the physicians and study subjects and blood was drawn for genomic DNA and biomarker studies. All data were double-entered into a database and systematically reviewed to minimize errors and include missing data. Results: A total of 1,000 subjects (460 RAP, 540 CP) and 695 controls who completed consent forms and questionnaires and donated blood samples comprised the final dataset. Data were organized according to diagnosis, supporting documentation, etiological classification, clinical signs and symptoms (including pain patterns and duration, and quality of life), past medical history, family history, environmental exposures (including alcohol and tobacco use), medication use and therapeutic interventions. Upon achieving the target enrollment, data were organized and classified to facilitate future analysis. The approaches, rationale and datasets are described, along with final demographic results. Conclusion: The NAPS2 consortium has successfully completed a prospective ascertainment of 1,000 subjects with RAP and CP from the USA. These data will be useful in elucidating the environmental, metabolic and genetic conditions, and to investigate the complex interactions that underlie RAP and CP.

© 2008 S. Karger AG, Basel and IAP


  

Author Contacts

David C. Whitcomb, MD, PhD
UPMC Presbyterian, M2 C-Wing
200 Lothrop Street, Pittsburgh, PA 15213 (USA)
Tel. +1 412 648 9604, Fax +1 412 383 7236
E-Mail whitcomb@pitt.edu

  

Article Information

Received: November 5, 2007
Accepted after revision: February 21, 2008
Published online: September 3, 2008
Number of Print Pages : 12
Number of Figures : 0, Number of Tables : 7, Number of References : 35

  

Publication Details

Pancreatology

Vol. 8, No. 4-5, Year 2008 (Cover Date: October 2008)

Journal Editor: Urrutia R. (Rochester, Minn.)
ISSN: 1424–3903 (Print), eISSN: 1424–3911 (Online)

For additional information: http://www.karger.com/PAN


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 11/5/2007
Accepted: 2/21/2008
Published online: 9/3/2008
Issue release date: October 2008

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 7

ISSN: 1424-3903 (Print)
eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Somogyi L, Martin SP, Ulrich CD: Recurrent acute pancreatitis. Curr Treat Options Gastroenterol 2001;4:361–368.
  2. Steer ML, Waxman I, Freedman S: Chronic pancreatitis. N Engl J Med 1995;332:1482–1490.
  3. Etemad B, Whitcomb DC: Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology 2001;120:682–707.
  4. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, et al: Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996;14:141–145.
  5. Whitcomb DC: Hereditary pancreatitis: new insights into acute and chronic pancreatitis. Gut 1999;45:317–322.
  6. Audrezet MP, Chen JM, Le Marechal C, Ruszniewski P, Robaszkiewicz M, Raguenes O, et al: Determination of the relative contribution of three genes – the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene – to the etiology of idiopathic chronic pancreatitis. Eur J Hum Genet 2002;10:100–106.
  7. Bernardino AL, Guarita DR, Mott CB, Pedroso MR, Machado MC, Laudanna AA, et al: CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients. JOP 2003;4:169–177.

    External Resources

  8. Ockenga J, Stuhrmann M, Ballmann M, Teich N, Keim V, Dork T, et al: Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are associated with recurrent or chronic idiopathic pancreatitis. Am J Gastroenterol 2000;95:2061–2067.
  9. Applebaum-Shapiro SE, Finch R, Pfützer RH, Hepp LA, Gates L, Amann S, et al: Hereditary pancreatitis in North America: The Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study. Pancreatology 2001;1:439–443.
  10. Whitcomb DC: Conference report: Pittsburgh Pancreasfest 2005. Pancreatology 2005;6:138–140.
  11. Sarner M, Cotton PB: Classification of pancreatitis. Gut 1984;25:756–759.
  12. Bradley KA, Boyd-Wickizer J, Powell SH, Burman ML: Alcohol screening questionnaires in women: a critical review. JAMA 1998;280:166–171.
  13. National Center for Health Statistics, Health, United States, 2006; with Chartbook on Trends in the Health of Americans. Hyattesville, 2006.
  14. Warshaw A, Banks PA, Femandez-del Castillo C: AGA technical review: treatment of pain in chronic pancreatitis. Gastroenterology 1998;115:765–776.
  15. Ammann RW, Muellhaupt B, Group ZPS: The natural history of pain in alcoholic chronic pancreatitis. Gastroenterology 1999;116:1132–1140.
  16. Bloechle C, Izbicki JR, Knoefel WT, Kuechler T, Broelsch CE: Quality of life in chronic pancreatitis – results after duodenum-preserving resection of the head of the pancreas. Pancreas 1995;11:77–85.
  17. Whitcomb DC, Barmada MM: A systems biology approach to genetic studies of pancreatitis and other complex diseases. Cell Mol Life Sci 2007;64:1763–1777.
  18. Whitcomb DC, Aoun E, Vodovotz Y, Clermont G, Barmada MM: Evaluating disorders with a complex genetics basis: the future role of meta-analysis and systems biology. Dig Dis Sci 2005;50:2195–2202.
  19. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG: Replication validity of genetic association studies. Nat Genet 2001;29:306–309.
  20. Ioannidis JP, Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG: Genetic associations in large versus small studies: an empirical assessment. Lancet 2003;361:567–571.
  21. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006;314:1461–1463.
  22. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al: Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 2007;39:596–604.
  23. Whitcomb DC: Mechanisms of disease: advances in understanding the mechanisms leading to chronic pancreatitis. Nat Clin Pract Gastroenterol Hepatol 2004;1:46–52.
  24. Manolio TA, Bailey-Wilson JE, Collins FS: Genes, environment and the value of prospective cohort studies. Nat Rev Genet 2006;7:812–820.
  25. Whitcomb DC: Value of genetic testing in management of pancreatitis. Gut 2004;53:1710–1717.
  26. Schneider A, Pfützer RH, Barmada MM, Slivka A, Martin J, Whitcomb DC: Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis – a preliminary report from the United States. Dig Dis Sci 2003;48:1110–1115.
  27. Schneider A, Pogue-Geile K, Barmada MM, Myers-Fong E, Thompson BS, Whitcomb DC: Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-α) promoter region or the TNF receptor 1 (TNFR1) gene. Genet Med 2003;5:120–125.
  28. Oruc N, Lamb J, Kutlu OC, Barmada MM, Money ME, Slivka A, et al: The functional angiotensin-converting enzyme gene I/D polymorphism does not alter susceptibility to chronic pancreatitis. JOP 2004;5:457–463.

    External Resources

  29. Schneider A, Barmada MM, Slivka A, Martin JA, Whitcomb DC: Analysis of tumor necrosis factor-α, transforming growth factor-β, interleukin-10, and interferon-γ polymorphisms in patients with alcoholic chronic pancreatitis. Alcohol 2004;32:19–24.
  30. Schneider A, Togel S, Barmada MM, Whitcomb DC: Genetic analysis of the glutathione S-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis. J Gastroenterol 2004;39:783–787.
  31. Schneider A, Lamb J, Barmada MM, Cuneo A, Money ME, Whitcomb DC: Keratin 8 mutations are not associated with familial, sporadic and alcoholic pancreatitis in a population from the United States. Pancreatology 2005;6:103–108.
  32. Schneider A, Lawrence EC, Barmada MM, Norris JM, Hamman RF, Marshall JA, et al: The SPINK1 N34S mutation is not associated with type 2 diabetes mellitus in a population of the USA. Diabet Med 2005;22:744–748.
  33. Zeh HJ, Winikoff S, Landsittel DP, Gorelik E, Marrangoni AM, Velikokhatnaya L, et al: Multianalyte profiling of serum cytokines for detection of pancreatic cancer. Cancer Biomark 2005;1:259–269.
  34. Sass DA, Papachristou GI, Lamb J, Barmada MM, Brand RE, Money ME, et al: The MCP-1 -2518 A/G polymorphism is not a susceptibility factor for chronic pancreatitis. Pancreatology 2006;6:297–300.
  35. Bhat YM, Papachristou GI, Park JS, Lamb J, Slivka A, Whitcomb DC: Functional polymorphisms of the GSTT-1 gene do not predict the severity of acute pancreatitis in the United States. Pancreatology 2007;7:180–186.