title: Common SPINK-1 mutations do not predispose to the development of non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is common in obese and diabetics. Serine protease inhibitor Kazal-1 (SPINK-1) protein is highly expressed in the liver and adipose tissue of diabetic and obese suggesting its role in NAFLD. SPINK-1 also behaves as an acute phase reactant protein. Some genetic factors including the genetic variations in SPINK-1 protein have been linked to chronic pancreatitis and diabetes. We therefore hypothesized that SPINK-1 mutations might be a risk factor for the development of NAFLD.
  
  
  METHODS
  Liver biopsy proven fifty NAFLD cases (20 steatohepatitis, 30 diffuse fatty liver disease and 44 healthy controls were included to the study. Liver function tests were measured. Body mass index was calculated. Insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Common genetic mutations in the third exon of SPINK-1 gene were analyzed by direct sequencing method.
  
  
  RESULTS
  We found two cases with a SNP at N34S location in NAFLD group (allele frequency %4). One subject with diffuse fatty liver disease and other with liver cirrhosis due to NAFLD had N34S mutation. No SNPs were detected in healthy controls. In conclusions, in limited number of patients SPINK-1 mutations were not considered as a risk factor alone for NAFLD development.
authors.affiliation: Department of Gastroenterology, Ege University, Faculty of Medicine, Izmir, Turkey. nevintr@yahoo.com
authors.forename: Nevin
authors.initials: N
authors.lastname: Oruc
authors.forename: Omer
authors.initials: O
authors.lastname: Ozutemiz
authors.forename: Afig
authors.initials: A
authors.lastname: Berdeli
authors.forename: Galip
authors.initials: G
authors.lastname: Ersoz
authors.forename: Fulya
authors.initials: F
authors.lastname: Gunsar
authors.forename: Zeki
authors.initials: Z
authors.lastname: Karasu
authors.forename: Tankut
authors.initials: T
authors.lastname: Ilter
authors.forename: Yucel
authors.initials: Y
authors.lastname: Batur
authors.forename: Ulus Salih
authors.initials: US
authors.lastname: Akarca
mesh_terms: D001706:Biopsy; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014421:Turkey
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic