Premium
The UCP 2 ‐866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis.
Author(s) -
Fares Roberta,
Petta Salvatore,
Lombardi Rosa,
Grimaudo Stefania,
Dongiovanni Paola,
Pipitone Rosaria,
Rametta Raffaela,
Fracanzani Anna Ludovica,
Mozzi Enrico,
Craxì Antonio,
Fargion Silvia,
Sesti Giorgio,
Valenti Luca
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12707
Subject(s) - medicine , steatosis , genotype , endocrinology , nonalcoholic fatty liver disease , steatohepatitis , insulin resistance , biology , type 2 diabetes , fatty liver , diabetes mellitus , genetics , gene , disease
Background & Aims Uncoupling protein 2 ‐ UCP 2 ‐ regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The −866 G>A UCP 2 promoter region polymorphism has been linked to insulin resistance and lipid metabolism. The aim of this study was to assess whether the −866 G>A UCP 2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP 2 expression. Methods We considered 688 Italian patients who underwent liver biopsy for suspected NASH, and 232 healthy controls. The UCP2 −866 G>A polymorphism was determined by allele specific oligonucleotide probes, hepatic UCP2 mRNA levels by quantitative real‐time PCR. Results UCP2 A/A genotype was associated with a reduced risk of nonalcoholic steatohepatitis (Odds Ratio 0.49, 95% C.I. 0.26–0.90; P = 0.02; adjusted for age, sex, BMI, impaired fasting glucose or diabetes, PNPLA3 I148M alleles and recruitment centre). The A/A genotype was associated with reduced risk of steatosis grade G2–G3 and nonalcoholic steatohepatitis in patients without ( P = 0.003 and P = 0.01 respectively), but not in those with ( P = NS) impaired fasting glucose/diabetes. The UCP2 A/A genotype was associated with higher hepatic UCP2 mRNA levels (adjusted P = 0.008). Concerning the metabolic traits, the UCP2 A/A genotype was associated with higher total serum cholesterol levels (adjusted P = 0.03), but not with serum HDL, triglycerides or impaired fasting glucose/diabetes. Conclusions UCP 2 −866 A/A genotype is associated with increased hepatic UCP 2 expression and reduced risk of nonalcoholic steatohepatitis, particularly in subjects with normal fasting glucose.