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The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls.
BMC Gastroenterol 2012; 12:111BG

Abstract

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.

Authors+Show Affiliations

Department of Internal Medicine, Università degli Studi Milano, UO Medicina Interna 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. luca.valenti@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22898488

Citation

Valenti, Luca, et al. "The I148M PNPLA3 Polymorphism Influences Serum Adiponectin in Patients With Fatty Liver and Healthy Controls." BMC Gastroenterology, vol. 12, 2012, p. 111.
Valenti L, Rametta R, Ruscica M, et al. The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. BMC Gastroenterol. 2012;12:111.
Valenti, L., Rametta, R., Ruscica, M., Dongiovanni, P., Steffani, L., Motta, B. M., ... Fargion, S. (2012). The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. BMC Gastroenterology, 12, p. 111.
Valenti L, et al. The I148M PNPLA3 Polymorphism Influences Serum Adiponectin in Patients With Fatty Liver and Healthy Controls. BMC Gastroenterol. 2012 Aug 16;12:111. PubMed PMID: 22898488.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls. AU - Valenti,Luca, AU - Rametta,Raffaela, AU - Ruscica,Massimiliano, AU - Dongiovanni,Paola, AU - Steffani,Liliana, AU - Motta,Benedetta Maria, AU - Canavesi,Elena, AU - Fracanzani,Anna Ludovica, AU - Mozzi,Enrico, AU - Roviaro,Giancarlo, AU - Magni,Paolo, AU - Fargion,Silvia, Y1 - 2012/08/16/ PY - 2012/03/05/received PY - 2012/08/07/accepted PY - 2012/8/18/entrez PY - 2012/8/18/pubmed PY - 2013/4/12/medline SP - 111 EP - 111 JF - BMC gastroenterology JO - BMC Gastroenterol VL - 12 N2 - 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. SN - 1471-230X UR - https://www.unboundmedicine.com/medline/citation/22898488/The_I148M_PNPLA3_polymorphism_influences_serum_adiponectin_in_patients_with_fatty_liver_and_healthy_controls_ L2 - https://bmcgastroenterol.biomedcentral.com/articles/10.1186/1471-230X-12-111 DB - PRIME DP - Unbound Medicine ER -