Therapeutic role of interleukin-1 receptor antagonist in pancreatic diseases: mendelian randomization study.

Shuai Yuan, Yuyang Miao, Xixian Ruan, Jie Chen, Xue Li, Susanna C Larsson

Journal: Frontiers in immunology 2023;14():1240754

PMID: 37781392

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Abstract

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 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, =0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, =2.93×10) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, =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.

Address: Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Medicine, Karolinska Institutet, Huddinge, Sweden.; Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China.; Department of Gastroenterology, Central South University, Changsha, China.; Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

DOI: 10.3389/fimmu.2023.1240754

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https://medlineplus.gov/pancreaticcancer.html

MeSH Terms: Humans, Interleukin 1 Receptor Antagonist Protein, Acute Disease, Mendelian Randomization Analysis, Receptors, Interleukin-1, Pancreatitis, Chronic, Pancreatic Neoplasms