title: Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  An association between nonalcoholic fatty liver disease (NAFLD) and the insulin resistance (IR) syndrome exists. Familial clustering of IR may support a genetic predisposition to NAFLD or cryptogenic cirrhosis (CC).
  
  
  METHODS
  Patients with NAFLD (n = 20) and healthy controls (n = 20) matched for age, sex, and body mass index with at least 4 living relatives and 2 generations of lineage participated in a familial aggregation study. A medical history was obtained from each subject and confirmed with first-degree family members.
  
  
  RESULTS
  NAFLD patients were more likely to have cirrhosis (odds ratio [OR] = 12.0), cardiac disease (OR, 3.0), hyperlipidemia (OR, 12.1), diabetes mellitus (DM) (OR, 9.1), renal stones (OR, 4.1), and arthritis (OR, 6.1). IR (P = .042) (the primary dependent variable) and DM (P = .013) were noted in their first-degree relatives. A trend for familial clustering of NAFLD or CC (P = .059) with a maternal linkage for disease expression also may exist. Cholelithiasis (P = .047), presumed NAFLD and/or CC (P = .049), and a trend toward IR (P = .07) were noted in the mothers, but not the fathers, of patients with NAFLD. An increased risk of DM (OR, 4.2; 95% confidence interval, 1.26-18.7; P = .013), IR (OR, 2.86; 95% confidence interval, 1.02-9.38; P = .042), and smoking (OR, 3.41; 95% confidence interval, 1.43-9.07; P = .003) was observed in first-degree relatives of NAFLD patients. No significant survival difference was observed between family cohorts.
  
  
  CONCLUSIONS
  Familial clustering and a potential maternal linkage for IR support a genetic predisposition for NAFLD. Alternatively, the presence of suppressor genes modifying the expression of IR in paternal lineage warrants further investigation.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA. manal.abdelmalek@duke.edu
authors.forename: Manal F
authors.initials: MF
authors.lastname: Abdelmalek
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shuster
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Nabih R
authors.initials: NR
authors.lastname: Asal
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D016000:Cluster Analysis; D005234:Fatty Liver / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006304:Health Status; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors