Results: We found that TG (P=0.004) and LDL-C (P=0.02) but not HDL-C GWA SNP sets were enriched in NAFLD. We identified 58 pathways that were enriched in lipid GWAS data. Three of these were also enriched in the NAFLD GWAS (N=7,

126) and one, FXR/RXR activation, also showed significant enrichment in the second independent NAFLD GWAS (N=3, 124). None of the three Doxorubicin in vitro original NAFLD enriched pathways were enriched for associations in control publically available GWAS analyses of diastolic and systolic blood pressure (N=275, 000), body mass index (N=249, 796), and waist to hip ratio (N=77, 167) suggesting that the enrichment was specific to NAFLD. Genes associated with NAFLD (P<0.05) in FXR/RXR activation fell into three functional categories: (1)VLDL Assembly: MTTP, APOB, APOC3, (2) Nuclear Related Processes: PPAR-a, HNF1 a, NR0B2/SHP and (3) Hepatic Transport: MRP2, AE2, ABCG8, ABCG5, OAT2. Conclusions: Using a novel approach, we found that human genetic variation in or near genes involved in FXR/RXR activation affects both blood lipids and NAFLD in humans. These results suggest that genes that play a role in lipoprotein assembly, nuclear receptor biology, and hepatic transport when altered may affect NAFLD and thus could provide possible therapeutic targets for NAFLD prevention or treatment. Disclosures:

The following people have nothing to disclose: Yindra M. Puentes, Corey Opaganib cost C. Powell, Laura M. Yerges-Armstrong, Mary F. Feitosa, Lawrence F. Bielak, Albert V. Smith, Tamara B. Harris, Jiankang Liu, Solomon K. Musani, Ingrid B. Borecki, Patricia A. Peyser, Elizabeth K. Speliotes Increased circulating soluble CD36 (sCD36), a cell-free form of fatty acid translocase CD36, clusters with insulin resistance and surrogate markers of fatty liver in population studies but no evidence exists on its

relationship with hepatic fat content. The aim of the present study was to elucidate whether circulating sCD36 is linked to the amount of lipids within the liver in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. This study comprised an overall population of 399 patients (227 with NAFLD, 87 with CHC, and 85 with histologically normal liver [NL]) who underwent a liver MCE公司 biopsy either by a percutaneous route for diagnostic purposes or during programmed abdominal surgery for gastroplasty or cholecystectomy. Steatosis was graded by Kleiner histological scoring system. Serum sCD36 levels and hepatic CD36 expression were assessed by immunoassay and immunohistochemistry, respectively. In NAFLD patients, serum sCD36 levels were significantly higher in those with simple steatosis than in NL subjects (361.4 ± 286.4 versus 173.9 ± 137.4 pg/mL, respectively; P < 0.001) but not in patients with steatohepatitis (229.