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Background: Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon. This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia., Methods: We undertook a one-year, prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides. The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption, the presence of co-morbidities and any medications being taken. The patients' progression, etiological diagnosis, hospital stay and clinical and radiological severity were all recorded., Results: Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%); the remaining cases were of biliary (53%), idiopathic (26%), alcoholic (11%) or other (5%) origin. Compared with these remaining cases, the patients with hypertriglyceridemia were significantly younger, had more relapses, and more often had diabetes mellitus. They usually consumed alcohol or consumed it excessively on the days before admission. Also, the ε4 allele of the APOE gene was more common in this group (P<0.05)., Conclusion: One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and, especially, alcohol consumption.