O-20 ASSOCIATION BETWEEN UNCOUPLING PROTEIN 3 POLYMORPHISMS AND NONALCOHOLIC FATTY LIVER DISEASE AND METABOLIC SYNDROME

Introduction

Genetic variants in the uncoupling protein 3 (UCP3) gene have been associated with obesity, type 2 diabetes and atherogenic lipid profile, with conflicting results.

Objective

Our study evaluated the possible association between UCP3 single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in NAFLD patients.

Methods

UCP3 SNPs rs1726745, rs3781907 and rs11235972 were genotyped in 158 biopsy-proven NAFLD patients. Patients were evaluated according to the presence of nonalcoholic fatty liver (NAFL) or NASH and, according to the absence or presence of MetS. Statistics were performed with JMP, R and SHEsis software's.

Results

The TT genotype of rs1726745 was protective for MetS (OR=0.18; 95% CI=0.05-0.61; p=0.006) and was associated with lower body mass index (BMI) in the general sample (p=0.01) and in the NASH group (p=0.02). The rs1726745-T was associated with lower values of AST (p=0.001), ALT (p=0.0002), triglycerides (p=0.01) and total cholesterol (p=0.02) in the general sample. There were lower values of aminotransferases strictly in individuals with NASH (AST, p=0.002; ALT, p=0.0007) and with MetS (AST, p=0.002; ALT, p=0.001). The rs3781907-G was associated with lower GGT values (p=0.002) in the general sample and in the NASH group (p=0.004) and with MetS group (p=0.003) and, with protection for advanced fibrosis (OR=0.25; 95% CI=0.08-0.69; p=0.01).The rs11235972-A was associated with lower GGT values (p=0.006) in the general sample and in the NASH group (p=0.01) and with MetS group (p=0.005), with fibrosis absence (OR=0.34; 95% CI=0.14-0.80; p=0.01) and protection for advanced fibrosis (OR=0.17; 95% CI=0.03-0.56; p=0.01). The TAA haplotype was protective for NASH (OR=0.01; 95% CI=0.00-0.12; p=0.002) and TGG haplotype was protective for MetS (OR=0.22; 95% CI=0.07-0.69; p=0.01).

Conclusion

UCP3 variants were associated with protection against NASH and MetS, in addition to lower values of liver enzymes, lipid profile, BMI and, lesser fibrosis severity in the studied population.