Objectives: The aim of the present study was to evaluate whether the lipin1 rs13412852 C>T polymorphism is associated with nonalcoholic steatohepatitis and fibrosis in pediatric Italian patients with nonalcoholic fatty liver disease (NAFLD).
Methods: A total of 142 untreated, consecutive children and 115 adults with biopsy-proven NAFLD and 337 healthy controls without steatosis were studied. Liver histology was assessed by the NAFLD activity score and the rs13412852 polymorphism by a 5′ nuclease Taqman assay.
Results: Homozygosity for the rs13412852 T allele was underrepresented in pediatric, but not adult, patients with NAFLD compared with healthy controls (7% vs 14%; odds ratio [OR] 0.58, 95% confidence interval [CI] 0.35–0.91), and it was associated with lower triglycerides both in pediatric patients and healthy controls (P ≤ 0.01). Affected children carrying the rs13412852 TT genotype had a trend for a lower prevalence of nonalcoholic steatohepatitis, and significantly less severe liver damage, as indicated by NAFLD activity score severity (P = 0.026) and a lower prevalence of liver fibrosis (P = 0.012). The negative association between rs13412852 TT genotype and fibrosis was independent of Patatin-like phospholipase domain-containing-3 genotype and other clinical risk factors, including age, waist circumference, the presence of hyperglycemia, and alanine transaminase levels (OR 0.29; 95% CI 0.11–0.66), and it was confirmed at multivariate analysis in adults (OR 0.15; 95% CI 0.02–0.67).
Conclusions: Lipin1 rs13412852 single nucleotide polymorphism is associated with the severity of liver damage and fibrosis progression in pediatric patients with histological NAFLD.
*Department of Internal Medicine, Università degli Studi, Ospedale Maggiore Policlinico “Ca’ Granda” IRCCS, Milan
†Liver Unit, Rare Diseases Unit, “Bambino Gesù” Children's Hospital and Research Institute, Rome, Italy.
Address correspondence and reprint requests to Luca Valenti, Centro Malattie Metaboliche del Fegato, Department of Internal Medicine, Università degli Studi Fondazione Ca’ Granda IRCCS, Ospedale Maggiore Policlinico, Padiglione Granelli, Via F Sforza 35, 20122 Milan, Italy (e-mail: email@example.com).
Received 19 July, 2011
Accepted 29 November, 2011
The work was supported by the following grants: FIRST Università di Milano 2007, 2008 (L.V., S.F.); Ricerca corrente Ospedale Maggiore Policlinico 2006 and 2008 (L.V., S.F.); and Centro per lo Studio delle Malattie del Fegato e del Metabolismo.
The authors report no conflicts of interest.