Clinical and genetic determinants of severe acute pancreatitis: A genetic association study in the UK Biobank.

Abstract

The clinical severity of acute pancreatitis is unpredictable, ranging from self-limiting disease to life-threatening inflammation. The determinants of severe acute pancreatitis (SAP) are unclear. We aim to identify clinical variables and single nucleotide polymorphisms (SNP) associated with SAP. We used UK Biobank data to conduct a case-control clinical and genetic association study. Pancreatitis patients were identified through national hospital and mortality records across the United Kingdom. Clinical covariates and SAP were analyzed for associations. Genotyped data that included 35 SNPs were assessed for independent associations with SAP and SNP to SNP interaction. A total of 665 patients with SAP and 3304 non-SAP patients were identified. Male sex and older age increased odds of developing SAP (odds ratio [OR] 1.48; 95% confiden interval [CI] 1.24-1.78, P<0.0001) and (OR 1.23; 95% CI 1.17-1.29), P<0.0001), respectively. SAP was associated with diabetes (OR 1.46; 95% CI 1.15-1.86, P=0.002), chronic kidney disease (OR 1.74; 95% CI 1.26-2.42, P=0.001), and cardiovascular disease (OR 2.00; 95% CI 1.54-2.61, P=0.0001). A significant association was established between IL-10 rs3024498 and SAP (OR 1.24; 95% CI 1.09-1.41, P=0.0014). Epistasis analysis revealed that the odds of SAP was greater by an interaction between TLR 5 rs5744174 and Factor V rs6025 (ORinteraction 7.53; P=6.64×10-5 ). This study reports clinical risk factors for SAP. We also show evidence for an interaction between rs5744174 and rs6025 as determinants for SAP in addition to rs3024498 independently altering the severity of acute pancreatitis.