The Association between SOCS1-1656G>A Polymorphism, Insulin Resistance and Obesity in Nonalcoholic Fatty Liver Disease (NAFLD) Patients.

Suppressor of cytokine signaling (SOCS) proteins prevent uncontrolled cytokine signaling and appear to play a role in the pathological processes behind obesity and insulin resistance. The polymorphism of the gene (rs243330, -1656G>A) is associated with obesity and glucose sensitivity. To estimate the effect of this gene polymorphism on nonalcoholic fatty liver disease (NAFLD) susceptibility, we performed a study on 138 patients with ultrasound-confirmed NAFLD and 1000 healthy blood donors. The relationship between the SOCS1-1656G>A polymorphism and serum biochemical parameters in NAFLD was additionally investigated. The variant was genotyped using a dedicated TaqMan assay. The frequency of rs243330 polymorphism did not differ between patients and controls. However, in a cohort of obese individuals (BMI ≥ 30 kg/m) the occurrence of the G allele of the SOCS1-1656G>A polymorphism was strongly associated with NAFLD (odds ratio (OR) 1.6; 95% CI,1.1-2.5; = 0.009), and carriers of the AA genotype have lower risk of developing NAFLD (OR 0.4; 95% CI, 0.2-0.7; = 0.004). Overweight NAFLD patients who were carriers of GG genotypes had significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) values ( = 0.03 vs. AA), and the obese GG homozygotes had lower serum concertation of triglyceride (GG vs. AA; = 0.02). Serum liver enzyme activities were not modified by the presence of risk variants. In conclusion, the observed phenotype of overweight NAFLD patients with non-elevated levels of TG and HOMA-IR, which is associated with genetic variants of , provides a rationale for further research on the pathophysiology of fatty liver disease.