A new and highly prevalent keratin mutation in patients with liver disease

Abstract

Background: We previously described keratin 8 and 18 (K8/K18) mutations in liver explants of 467 patients with cirrhosis (17 of 467, 3.6%). These mutations were found in only 2 of 349 (0.6%) normal blood bank controls (p 0.7). Conclusion: Our previous and present data, collectively, show that unique and likely function-altering keratin mutations are present in 46 of 467 liver disease patients (9.9%), while 11 of 349 normal volunteers (3.2%) harbored such mutations (p=0.0001). The most common K8/K18 mutation to date is the newly identified K8 R340H (29 of 46 independent mutations; 63%) with the next most common mutation (K8 Gly61-to-Cys) accounting for 13% of the identified mutations. Hence, K8/K18 (particularly K8) mutations are emergmg as common genetic risks for developing liver cirrhosis, in the presence of additional environmental/genetic insults.