Pancreatic diseases represent a major, poorly treated health-care problem in the United States Unfortunately, once established the devastating effects of severe acute pancreatitis or chronic pancreatitis cannot be reversed. We believe true advances in the treatment of pancreatic disease, as in other diseases, rest in the early identification of at-risk individuals and in the prevention or limitation of the disease. Herein we propose a national study to determine the regional prevalence of major pancreatic diseases classified according to the TIGAR-O system, to determine the underlying genetic variations and immune markers associated with pancreatitis, and to develop a major biological and phenotypic resource for future investigations. This approach utilizes innovative, high-throughput gene analysis technologies to assist in genotype-phenotype correlation, prognostication and risk assessment.
Our Specific Aims are as follows.
Aim 1 : To establish a national network of centers with expertise in pancreatic disease for the recruitment and follow-up of patients with recurrent acute and chronic pancreatitis with spouse, age and race matched controls, and sib/parent controls, and to develop a biologic repository for further study.
Aim 2 : To determine the prevalence of known genetic variations and autoimmune markers associated with recurrent acute and chronic pancreatitis.
Aim 3 : To describe the interaction of environmental and genetic factors in the expression of the clinical manifestations of chronic pancreatitis and risk of pancreatic cancer. The results of these studies may result in the development new diagnostic tools that can be applied at the onset of symptoms, and rational therapy to prevent the development of those pancreatic diseases that we cannot currently cure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK061451-01
Application #
6462830
Study Section
Special Emphasis Panel (ZDK1-GRB-5 (J2))
Program Officer
Serrano, Jose
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$642,118
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Machicado, Jorge D; Amann, Stephen T; Anderson, Michelle A et al. (2017) Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities. Am J Gastroenterol 112:633-642
Zator, Zachary; Whitcomb, David C (2017) Insights into the genetic risk factors for the development of pancreatic disease. Therap Adv Gastroenterol 10:323-336
Whitcomb, David C (2016) Peering Into the ""Black Box"" of the Complex Chronic Pancreatitis Syndrome. Pancreas 45:1361-1364
Romagnuolo, Joseph; Talluri, Jyothsna; Kennard, Elizabeth et al. (2016) Clinical Profile, Etiology, and Treatment of Chronic Pancreatitis in North American Women: Analysis of a Large Multicenter Cohort. Pancreas 45:934-40
Li, Dalin; Achkar, Jean-Paul; Haritunians, Talin et al. (2016) A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition. Gastroenterology 151:724-32
Wilcox, C Mel; Yadav, Dhiraj; Ye, Tian et al. (2015) Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings. Clin Gastroenterol Hepatol 13:552-60; quiz e28-9
Smith, Jill P; Whitcomb, David C; Matters, Gail L et al. (2015) Distribution of cholecystokinin-B receptor genotype between patients with pancreatic cancer and controls and its impact on survival. Pancreas 44:236-42
Whitcomb, David C (2015) Innovation and hard work: The 2015 George E. Palade Medal Award Lecture. Pancreatology 15:611-5
LaRusch, Jessica; Jung, Jinsei; General, Ignacio J et al. (2014) Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. PLoS Genet 10:e1004376

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