title: Vitamin D is Not Associated With Severity in NAFLD: Results of a Paired Clinical and Gene Expression Profile Analysis.
abstract: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is complex. Vitamin D (VitD) has been implicated in NAFLD pathogenesis because it has roles in immune modulation, cell differentiation and proliferation, and regulation of inflammation. We evaluated the association of VitD levels, hepatic gene expression for VitD metabolizing genes, and NAFLD histological severity.
  
  
  
  Two adult cohorts, controls (n=39) and NAFLD (n=244), who underwent liver biopsy were compared. Two-sided t-tests or Wilcoxon's rank-sum tests for continuous predictors and chi-squared tests or Fisher's exact tests for categorical variables were used to analyze the association of VitD and NAFLD. Generalized linear models were used to analyze the association of VitD levels and VitD metabolizing genes with histological severity of NAFLD while adjusting for potential confounders and correcting for multiple comparisons.
  
  
  
  NAFLD patients were more likely than controls to have higher HbA1c (6.5±1.2 vs 5.9±1.0; P=0.009), a risk factor for VitD deficiency. However, no difference in VitD levels was observed between groups. VitD levels did not correlate with the severity of hepatic steatosis, lobular or portal inflammation, or ballooned hepatocytes after adjusting for confounding factors. Furthermore, no association was noted between VitD deficiency or differential expression of genes involved in VitD metabolism and severity of hepatic fibrosis or any other histologic feature of NAFLD.
  
  
  
  Neither VitD deficiency, nor hepatic expression of VitD-related genes, associate with the presence or histologic severity of NAFLD in patients. Hence, despite preclinical evidence implicating VitD in NAFLD pathogenesis, VitD deficiency does not appear to be associated with NAFLD severity in humans.
authors.affiliation: Division of Gastroenterology and Hepatology, Durham, North Carolina, USA.
authors.forename: Yuval A
authors.initials: YA
authors.lastname: Patel
authors.affiliation: Department of Electrical and Computer Engineering, Durham, North Carolina, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Henao
authors.affiliation: Division of Gastroenterology and Hepatology, Durham, North Carolina, USA.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Moylan
authors.affiliation: Department of Pathology, Duke University, Durham, North Carolina, USA.
authors.forename: Cynthia D
authors.initials: CD
authors.lastname: Guy
authors.affiliation: Division of Gastroenterology and Hepatology, Durham, North Carolina, USA.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Piercy
authors.affiliation: Division of Gastroenterology and Hepatology, Durham, North Carolina, USA.
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
authors.affiliation: Division of Gastroenterology and Hepatology, Durham, North Carolina, USA.
authors.forename: Manal F
authors.initials: MF
authors.lastname: Abdelmalek
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D003430:Cross-Sectional Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D000072467:Cytochrome P450 Family 2 / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D056918:Nuclear Receptor Coactivators / Q000235:genetics; D010281:Parathyroid Hormone / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000235:genetics; D047488:Retinoid X Receptors / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000453:epidemiology* / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics
chemical_list: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D053493:Cholestanetriol 26-Monooxygenase; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D006442:Glycated Hemoglobin; D056918:Nuclear Receptor Coactivators; D010281:Parathyroid Hormone; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D014807:Vitamin D; D014809:Vitamin D-Binding Protein; D065668:Vitamin D3 24-Hydroxylase; C579457:VDR protein, human; C517652:hemoglobin A1c protein, human; C104450:25-hydroxyvitamin D; C506833:CYP2R1 protein, human; C510163:CYP3A4 protein, human; C506831:CYP27A1 protein, human; C585549:CYP24A1 protein, human; C000600378:CYP27B1 protein, human