Association of UCP3 Polymorphisms with Nonalcoholic Steatohepatitis and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease Brazilian Patients.

Background: We investigated the possible association of uncoupling protein 3 gene ( UCP3 ) single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in nonalcoholic fatty liver disease (NAFLD) Brazilian patients. Methods: UCP3 SNPs rs1726745, rs3781907, and rs11235972 were genotyped in 158 biopsy-proven NAFLD Brazilian patients. Statistics was performed with JMP, R, and SHEsis softwares. Results: The TT genotype of rs1726745 was associated with less occurrence of MetS ( P  = 0.006) and with lower body mass index (BMI) in the entire NAFLD 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 entire NAFLD sample. Between groups, 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 elevation values in the entire NAFLD sample ( P  = 0.002), in the NASH group ( P  = 0.004), and with MetS group ( P  = 0.003) and with protection for advanced fibrosis ( P  = 0.01). The rs11235972-A was associated with lower GGT values in the entire NAFLD sample ( P  = 0.006) and in the NASH group ( P  = 0.01) and with MetS group ( P  = 0.005), with fibrosis absence ( P  = 0.01) and protection for advanced fibrosis ( P  = 0.01). The TAA haplotype was protective for NASH ( P  = 0.002), and TGG haplotype was protective for MetS ( P  = 0.01). Conclusion: UCP3 gene 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.