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| Content Provider | PubMed Central |
|---|---|
| Author | Whitcomb, David C. |
| Copyright Year | 2012 |
| Abstract | Chronic pancreatitis (CP) is defined by irreversible damage to the pancreas as a result of inflammation-driven pancreatic tissue destruction and fibrosis occurring over many years. The disorder is complex, with multiple etiologies leading to the same tissue pathology, and unpredictable clinical courses with variable pain, exocrine and endocrine organ dysfunction, and cancer. Underlying genetic variants are central CP susceptibility and progression. Three genes, with Mendelian genetic biology (PRSS1, CFTR, and SPINK1) have been recognized for over a decade, and little progress has been made since then. Furthermore, application of high-throughput genetic techniques, including genome-wide association studies (GWAS) and next generation sequencing (NGS) will provide a large volume of new genetic variants that are associated with CP, but with small independent effect that are impossible to apply in the clinic. The problem of interpretation is using the old framework of the germ theory of disease to understand complex genetic disorders. To understand these variants and translate them into clinically useful information requires a new framework based on modeling and simulation of physiological processes with or without genetic, metabolic and environmental variables considered at the cellular and organ levels, with integration of the immune system, nervous system, tissue injury and repair system, and DNA repair system. The North American Pancreatitis Study 2 (NAPS2) study was designed to capture this type of date and construct a time line to understand and later predict rates of disease progression from the initial symptom to end-stage disease. This effort is needed to target the etiology of pancreatic dysfunction beginning at the first signs of disease and thereby prevent the development of irreversible damage and the complications of CP. The need for a new framework and the rational for implementing it into clinical practice are described. |
| Related Links | http://dx.doi.org/10.3389/fphys.2012.00440 |
| Starting Page | 440 |
| File Format | |
| ISSN | 1664042X |
| e-ISSN | 1664042X |
| Journal | Frontiers in Physiology |
| Volume Number | 3 |
| Language | English |
| Publisher | Frontiers Media S.A. |
| Publisher Date | 2012-01-01 |
| Access Restriction | Open |
| Rights Holder | Frontiers Media S.A. |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) |
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