Quantitative trait locus analysis for chronic pancreatitis and diabetes mellitus in the WBN/Kob rat

A causative gene mutation is still undefined in approximately half of patie nts with hereditary pancreatitis, and no genetic factor has been identified in most patients with sporadic chronic pancreatitis. To identify a pancrea titis-associated gene, we performed a quantitative trait locus (QTL) analys is for the traits of chronic pancreatitis and diabetes mellitus in WBN/ Kob rats. We identified two highly significant QTLs for chronic pancreatitis a nd/or hyperinsulinemia on chromosomes 7 and X. These QTLs were located on c ompletely different chromosomal regions from those of causative genes that have been reported for human chronic pancreatitis: PRSS1, CFTR, and SPINK1. For these QTLs, prevalences of the WBN/Kob allele significantly increased in the rats with chronic pancreatitis. These findings indicate that chronic pancreatitis in WBN/Kob rats is controlled by multiple genes, and a geneti c analysis in WBN/Kob rats might be useful for gene targeting for human chr onic pancreatitis. (C) 2001 Academic Press.