The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis

Antonio Craxi, Stefania Grimaudo, Rosaria Maria Pipitone, Salvatore Petta, Raffaela Rametta, Rosa Lombardi, Roberta Fares, Paola Dongiovanni, Enrico Mozzi, Anna Ludovica Fracanzani, Giorgio Sesti, Luca Valenti, Silvia Fargion

Risultato della ricerca: Article

15 Citazioni (Scopus)

Abstract

Background & Aims: Uncoupling protein 2 - UCP2 - regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The -866 G>A UCP2 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 UCP2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 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: UCP2 -866 A/A genotype is associated with increased hepatic UCP2 expression and reduced risk of nonalcoholic steatohepatitis, particularly in subjects with normal fasting glucose.
Lingua originaleEnglish
pagine (da-a)1574-1580
Numero di pagine7
RivistaLiver International
Volume35
Stato di pubblicazionePublished - 2015

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Genetic Promoter Regions
Genotype
Fasting
Liver
Glucose
Lipid Metabolism
Alleles
Messenger RNA
Oligonucleotide Probes
Electron Transport
Serum
Insulin Resistance
Real-Time Polymerase Chain Reaction
Reactive Oxygen Species
Triglycerides
Odds Ratio
Cholesterol
Non-alcoholic Fatty Liver Disease
Lipids
Biopsy

All Science Journal Classification (ASJC) codes

  • Hepatology

Cita questo

The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis. / Craxi, Antonio; Grimaudo, Stefania; Pipitone, Rosaria Maria; Petta, Salvatore; Rametta, Raffaela; Lombardi, Rosa; Fares, Roberta; Dongiovanni, Paola; Mozzi, Enrico; Fracanzani, Anna Ludovica; Sesti, Giorgio; Valenti, Luca; Fargion, Silvia.

In: Liver International, Vol. 35, 2015, pag. 1574-1580.

Risultato della ricerca: Article

Craxi, A, Grimaudo, S, Pipitone, RM, Petta, S, Rametta, R, Lombardi, R, Fares, R, Dongiovanni, P, Mozzi, E, Fracanzani, AL, Sesti, G, Valenti, L & Fargion, S 2015, 'The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis', Liver International, vol. 35, pagg. 1574-1580.
Craxi, Antonio ; Grimaudo, Stefania ; Pipitone, Rosaria Maria ; Petta, Salvatore ; Rametta, Raffaela ; Lombardi, Rosa ; Fares, Roberta ; Dongiovanni, Paola ; Mozzi, Enrico ; Fracanzani, Anna Ludovica ; Sesti, Giorgio ; Valenti, Luca ; Fargion, Silvia. / The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis. In: Liver International. 2015 ; Vol. 35. pagg. 1574-1580.
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abstract = "Background & Aims: Uncoupling protein 2 - UCP2 - regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The -866 G>A UCP2 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 UCP2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 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: UCP2 -866 A/A genotype is associated with increased hepatic UCP2 expression and reduced risk of nonalcoholic steatohepatitis, particularly in subjects with normal fasting glucose.",
author = "Antonio Craxi and Stefania Grimaudo and Pipitone, {Rosaria Maria} and Salvatore Petta and Raffaela Rametta and Rosa Lombardi and Roberta Fares and Paola Dongiovanni and Enrico Mozzi and Fracanzani, {Anna Ludovica} and Giorgio Sesti and Luca Valenti and Silvia Fargion",
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pages = "1574--1580",
journal = "Liver International",
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T1 - The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis

AU - Craxi, Antonio

AU - Grimaudo, Stefania

AU - Pipitone, Rosaria Maria

AU - Petta, Salvatore

AU - Rametta, Raffaela

AU - Lombardi, Rosa

AU - Fares, Roberta

AU - Dongiovanni, Paola

AU - Mozzi, Enrico

AU - Fracanzani, Anna Ludovica

AU - Sesti, Giorgio

AU - Valenti, Luca

AU - Fargion, Silvia

PY - 2015

Y1 - 2015

N2 - Background & Aims: Uncoupling protein 2 - UCP2 - regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The -866 G>A UCP2 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 UCP2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 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: UCP2 -866 A/A genotype is associated with increased hepatic UCP2 expression and reduced risk of nonalcoholic steatohepatitis, particularly in subjects with normal fasting glucose.

AB - Background & Aims: Uncoupling protein 2 - UCP2 - regulates mitochondrial lipid fluxes and reactive oxygen species production by the respiratory chain. The -866 G>A UCP2 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 UCP2 polymorphism predisposes to nonalcoholic steatohepatitis in patients at risk, and the relationship with lipid metabolism and hepatic UCP2 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: UCP2 -866 A/A genotype is associated with increased hepatic UCP2 expression and reduced risk of nonalcoholic steatohepatitis, particularly in subjects with normal fasting glucose.

UR - http://hdl.handle.net/10447/160455

UR - http://www.wiley.com/bw/journal.asp?ref=1478-3223

M3 - Article

VL - 35

SP - 1574

EP - 1580

JO - Liver International

JF - Liver International

SN - 1478-3223

ER -