However, familial, epidemiological, and twin studies have suggest

However, familial, epidemiological, and twin studies have suggested that inherited factors may also play a pivotal role in determining the susceptibility to developing NASH.11-14 Single nucleotide polymorphisms (SNPs) in genes Lumacaftor in vitro involved in inflammation, insulin signaling, oxidative

stress, and fibrogenesis have been associated with the severity of liver damage in NAFLD,15-18 but these factors explain only a small portion of fibrosis variability. Recently, genome-wide association studies have identified as a strong determinant of liver fat an SNP in adiponutrin/patatin-like phospholipase domain-containing 3 (PNPLA3), rs738409 C>G, which encodes the I148M protein variant.19-21 The I148M SNP influences liver fat without affecting the body mass, dyslipidemia, or insulin resistance. Adiponutrin expression in the liver and adipose tissue is increased by carbohydrate feeding and a Western-type diet.22-24 Furthermore, it has lipase activity against triglycerides and thus is likely involved in energy mobilization and storage in lipid droplets.25 It has been reported that the 148M PNPLA3 allele is a loss-of-function variant that predisposes patients to steatosis by decreasing triglyceride hydrolysis in hepatocytes.26 We recently showed that the rs738409 PNPLA3 SNP was strongly associated

with severe steatosis, NASH, and the progression of liver fibrosis in a large series of Italian and UK patients with NAFLD.27 However, even though genetic factors Ensartinib order likely play a stronger role in NASH development in children, no data are available concerning the role of the PNPLA3 genotype in this setting. The aim of this study was to evaluate whether the rs738409 PNPLA3 SNP, encoding the functional I148M protein

variant, is associated with a predisposition to NASH and progressive liver fibrosis in a large series of Italian pediatric patients with a histological diagnosis of NAFLD and may represent a noninvasive early marker of advanced disease. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval; GGT, gamma-glutamyl transferase; HOMA-IR, homeostasis model assessment of insulin resistance; IGT, impaired glucose tolerance; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NS, not significant; MCE公司 OR, odds ratio; PNPLA3, patatin-like phospholipase domain-containing 3; SD, standard deviation; SNP, single nucleotide polymorphism. This prospective study included 149 consecutive untreated children and adolescents (93 males and 56 females) with biopsy-proven NAFLD who were referred to Bambino Gesù Children’s Hospital between May 2006 and November 2009. All patients were tested for secondary causes of steatosis such as alcohol abuse (≥140 g/week), total parenteral nutrition, and the use of drugs known to precipitate steatosis (e.g., valproate, amiodarone, and prednisone).

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