Pancreatitis: Facts and Fiction

Additional Research

Are there genetic variant patterns in pancreatitis patients?

To see if any variants found in research participants may be related to increased risk of pancreatitis, how often variants were identified in people with pancreatitis was compared with how often these variants were found in the general population. As has long been known, most variants represent harmless interpersonal variation, and so most variants were not found to be associated with disease. However, 15 variants were found to be more common in participants than expected, suggesting that they may be harmful.

Next, researchers looked for relationships between different variants within genes and between genes. They tested how often two variants occurred with each other in a single person with pancreatitis. As expected, some genetic variants were commonly found together in the same gene. This is because multiple genes or chunks of DNA tend to be inherited together. These variants that are near each other or in the same gene that are inherited together form what is called a haplotype. When a haplotype is associated with disease, typically only one variant is harmful. Knowing which variants are present in a disease-associated haplotype helps researchers determine which variant is harmful.

Last, combinations of variants in different genes were investigated. The findings suggested that variants in both protective and stress genes may co-occur more frequently in individuals with pancreatitis than the general population. For example, variants in the protective region GGT1 had co-occurrence with those in the risk region CFTR, as in the model described above. Support for their combined role in contributing to pancreatitis was found by examining what part of the pancreas these genes are active in. Both GGT1 and CFTR were found to be expressed in the duct of the pancreas. Because this was a small exploratory study, none of the co-occurrences reached statistical significance. Nevertheless, the biological plausibility of the findings provide valuable starting points for future larger studies.

How does this help your patients?

Scientific research forms the foundation of all successful clinical tests and treatments. To deliver the best possible individualized treatments for pancreatic disease, it’s important to first understand how certain genetic variants that make us unique might work together to increase risk. This study builds on previous basic research and lays some groundwork for further research studies.

The earlier stages of basic research can then be built upon to devise ways of helping patients in clinic. For example, later studies can involve identifying at-risk people earlier in their disease course, creating new diagnostic tools, developing new medications and ultimately, preventing the disease altogether. Ariel is committed to advancing pancreatitis genetics research in every stage of this pipeline to benefit the pancreatitis patient community.

References

Ellison M, Spagnolo D, Shelton C, Orlova E, LaRusch J, Whitcomb D, Haupt M. Complex genetics in pancreatitis: insights gained from a new candidate locus panel. Pancreas: July 9, 2020 – Volume Publish Ahead of Print – Issue – doi: 10.1097/MPA.0000000000001612 papancr