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Therapeutic role of interleukin-1 receptor antagonist in pancreatic diseases: mendelian randomization study
Shuai Yuan1, Yuyang Miao2,3, Xixian Ruan4
1Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Background:
The interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer.
Methods:
Genetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the IL1RN gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources.
Results:
Genetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97, P=0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, P=2.93×10-8) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, P=0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA.
Conclusion:
This study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.
Insights
Higher levels of interleukin-1 receptor antagonist (IL-1RA) are linked to reduced risks of acute pancreatitis, chronic pancreatitis, and pancreatic cancer. This suggests IL-1RA may offer therapeutic benefits for pancreatic diseases.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- The interleukin-1 (IL-1) pathway is implicated in various pancreatic diseases.
- Investigating the role of interleukin-1 receptor antagonist (IL-1RA) in pancreatitis and pancreatic cancer is crucial.
Approach:
- Utilized Mendelian randomization with genetic variants associated with IL-1RA levels.
- Employed summary-level data from UK Biobank and FinnGen for meta-analysis.
- Assessed associations between genetically predicted IL-1RA and pancreatic diseases.
Key Points:
- Genetically predicted higher IL-1RA levels showed a significant association with reduced risk for acute pancreatitis (OR 0.87, P=0.003).
- Higher IL-1RA levels were strongly linked to lower risk of chronic pancreatitis (OR 0.73, P=2.93×10⁻⁸).
- A reduced risk of pancreatic cancer was also observed with higher IL-1RA levels (OR 0.86, P=0.009).
Conclusions:
- IL-1RA appears to have a protective effect against acute pancreatitis, chronic pancreatitis, and pancreatic cancer.
- These findings highlight the potential therapeutic value of IL-1RA in managing pancreatic diseases.
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