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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1574-1580
Number of pages7
JournalLiver International
Volume35
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

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

Keywords

  • Genetic polymorphism
  • Lipid metabolism
  • Liver
  • Mitochondria
  • Nonalcoholic steatohepatitis
  • Uncoupling protein-2

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

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

In: Liver International, Vol. 35, No. 5, 01.05.2015, p. 1574-1580.

Research output: Contribution to journalArticle

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. / The UCP2 -866 G>A promoter region polymorphism is associated with nonalcoholic steatohepatitis. In: Liver International. 2015 ; Vol. 35, No. 5. pp. 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.",
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author = "Roberta Fares and Salvatore Petta and Rosa Lombardi and Stefania Grimaudo and Paola Dongiovanni and Rosaria Pipitone and Raffaela Rametta and Fracanzani, {Anna Ludovica} and Enrico Mozzi and Antonio Crax{\`i} and Silvia Fargion and Giorgio Sesti and Luca Valenti",
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AU - Fares, Roberta

AU - Petta, Salvatore

AU - Lombardi, Rosa

AU - Grimaudo, Stefania

AU - Dongiovanni, Paola

AU - Pipitone, Rosaria

AU - Rametta, Raffaela

AU - Fracanzani, Anna Ludovica

AU - Mozzi, Enrico

AU - Craxì, Antonio

AU - Fargion, Silvia

AU - Sesti, Giorgio

AU - Valenti, Luca

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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.

KW - Genetic polymorphism

KW - Lipid metabolism

KW - Liver

KW - Mitochondria

KW - Nonalcoholic steatohepatitis

KW - Uncoupling protein-2

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