Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease.
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.
Abdelmalek
Manal F
MF
Division of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA. manal.abdelmalek@duke.edu
Liu
Chen
C
Shuster
Jonathan
J
Nelson
David R
DR
Asal
Nabih R
NR
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