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

Frontiers in Immunology

Immunology

Xue Li¹  Jie Chen¹  Xixian Ruan²  Yuyang Miao³  Shuai Yuan⁴  Susanna C. Larsson⁵ 

[1] 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;Department of Gastroenterology, Central South University, Changsha, China;Department of Medicine, Karolinska Institutet, Huddinge, Sweden;Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China;Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;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;

关键词: interleukin-1 receptor antagonist;    mendelian randomization;    pancreatic disease;    acute pancreatitis (AP);    chronic pancreatitis;    pancreatic cancer;   

DOI  :  10.3389/fimmu.2023.1240754

 received in 2023-06-15, accepted in 2023-08-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe 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.MethodsGenetic 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.ResultsGenetically 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.ConclusionThis study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.

【 授权许可】

Unknown   
Copyright © 2023 Yuan, Miao, Ruan, Chen, Li and Larsson