期刊论文详细信息
BMC Gastroenterology
The i148m Pnpla3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls
Silvia Fargion3  Paolo Magni2  Giancarlo Roviaro1  Enrico Mozzi1  Anna Ludovica Fracanzani3  Elena Canavesi3  Benedetta Maria Motta3  Liliana Steffani2  Paola Dongiovanni3  Massimiliano Ruscica2  Raffaela Rametta3  Luca Valenti3 
[1] Department of Surgery, Università degli Studi Milano, Ospedale Maggiore “Ca’ Granda” Fondazione Policlinico IRCCS, Milan, Italy;Department of Endocrinology, Pathophysiology and Applied Biology, Università degli Studi Milano, Milan, Italy;Department of Internal Medicine, Università degli Studi Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
关键词: Steatosis;    Pnpla3;    Nonalcoholic steatohepatitis;    Nonalcoholic fatty liver disease;    Genetics;    Gender;    Fibrosis;    Chronic hepatitis C;    Adiponutrin;    Adiponectin;   
Others  :  1121886
DOI  :  10.1186/1471-230X-12-111
 received in 2012-03-05, accepted in 2012-08-07,  发布年份 2012
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【 摘 要 】

Background

Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls.

Methods

To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ) genotype. PNPLA3 rs738409 (I148M) and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT) of 35 obese subjects undergoing bariatric surgery.

Results

Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148 M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p = 0.03), and in healthy subjects (p = 0.04). At multivariate analysis, PNPLA3 148 M alleles were associated with low adiponectin levels (<6 mg/ml, median value) independently of NAFLD diagnosis, age, gender, BMI, and ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148 M allele). The p.148 M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p < 0.05) even in the absence of NASH. In contrast, in CHC, characterized by adiponectin resistance, low adiponectin was associated with male gender and steatosis, but not with PNPLA3 and ADIPOQ genotypes and viral features.

Conclusions

The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum adiponectin levels. Modulation of serum adiponectin might be involved in mediating the susceptibility to steatosis, NASH, and hepatocellular carcinoma in carriers of the 148 M PNPLA3 variant without CHC, with potential therapeutic implications.

【 授权许可】

   
2012 Valenti et al.; licensee BioMed Central Ltd.

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