Genetics of Pancreatitis
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The association between alcohol misuse and chronic pancreatitis (CP) has been recognized for a long time. CP is a multifactorial and a complex disease, and the combination of genetic, environmental, and metabolic factors contributes to its development. Extensive research has been done to clarify the genetic factors. Candidate-gene approaches have focused on variants in the alcohol metabolizing enzymes (alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2)) and known pancreatitis susceptibility genes such as cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), and chymotrypsin C (CTRC). It has been increasingly acknowledged that these previously known pancreatitis susceptibility genes identified in non-alcoholic (hereditary and idiopathic) CP also play a role in alcoholic CP. In addition, recent genome-wide association studies have identified new risk loci: the polymorphisms in the PRSS1-PRSS2 and the CLDN2-RIPPLY1-MORC4 loci and the inversion in the CTRB1-CTRB2 locus. The genetic alterations might at least in part explain a long-standing unsolved question: why only a small portion of heavy drinkers develop pancreatitis.
KeywordsAlcohol dehydrogenase Aldehyde dehydrogenase CTRB CTRC Genome-wide association study Pancreatitis PRSS1 PRSS2 SPINK1 Trypsin
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- 24.Perri F, Piepoli A, Stanziale P, et al. Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the cationic trypsinogen (PRSS1) gene, and the serine protease inhibitor, Kazal type 1 (SPINK1) gene in patients with alcoholic chronic pancreatitis. Eur J Hum Genet. 2003;11:687–92.CrossRefGoogle Scholar
- 38.Audrézet MP, Chen JM, Le Maréchal C, et al. Determination of the relative contribution of three genes-the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis. Eur J Hum Genet. 2002;10:100–6.CrossRefGoogle Scholar
- 45.Weiss FU, Schurmann C, Guenther A, et al. Fucosyltransferase 2 (FUT2) non-secretor status and blood group B are associated with elevated serum lipase activity in asymptomatic subjects, and an increased risk for chronic pancreatitis: a genetic association study. Gut. 2015;64:646–56.CrossRefGoogle Scholar