The UCP2 ‐866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis. (20th November 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Liver international. Volume 35:Number 5(2015:May)
• Page Start: 1574
• Page End: 1580
• Publication Date: 2014-11-20
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12707
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12707-abs-0001"> <title>Abstract</title> <sec id="liv12707-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Uncoupling protein 2 ‐ UCP2 ‐ regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The −866 G>A <italic>UCP2</italic> 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 <italic>UCP2</italic> polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 expression.</p> </sec> <sec id="liv12707-sec-0002" sec-type="section"> <title>Methods</title> <p>We considered 688 Italian patients who underwent liver biopsy for suspected NASH, and 232 healthy controls. The <italic>UCP2</italic> −866 G>A polymorphism was determined by allele specific oligonucleotide probes, hepatic UCP2 mRNA levels by quantitative real‐time PCR.</p> </sec> <sec id="liv12707-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>UCP2</italic> A/A genotype was associated with a reduced risk of nonalcoholic steatohepatitis (Odds Ratio 0.49, 95% C.I. 0.26–0.90; <italic>P</italic> = 0.02; adjusted for age, sex, BMI, impaired fasting glucose or diabetes, <italic>PNPLA3</italic> 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 (<italic>P</italic> = 0.003 and <italic>P</italic> = 0.01 respectively), but not in those with (<italic>P </italic>= NS) impaired fasting glucose/diabetes. The <italic>UCP2</italic> A/A genotype was associated with higher hepatic UCP2 mRNA levels (adjusted <italic>P</italic> = 0.008). Concerning the metabolic traits, the <italic>UCP2</italic> A/A genotype was associated with higher total serum cholesterol levels (adjusted <italic>P</italic> = 0.03), but not with serum HDL, triglycerides or impaired fasting glucose/diabetes.</p> </sec> <sec id="liv12707-sec-0004" sec-type="section"> <title>Conclusions</title> <p> <italic>UCP2</italic> −866 A/A genotype is associated with increased hepatic UCP2 expression and reduced risk of nonalcoholic steatohepatitis, particularly in subjects with normal fasting glucose.</p> </sec> </abstract>