title: Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease (NAFLD) and their relation with the disease severity.
  
  
  METHODS
  A total of 136 patients with NAFLD and 64 healthy individuals were studied. Liver biopsy was performed in 91 patients. Six tag SNPs showing a minor allele frequency > 10% (rs1554483 C/G; rs11932595 A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G and rs4864548 A/G) encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r(2) > 0.8) were genotyped.
  
  
  RESULTS
  rs11932595 and rs6843722 showed significant associations with NAFLD (empiric P = 0.0449 and 0.023, respectively). A significant association was also observed between clinical or histologic spectrum of NAFLD and rs1554483 (empiric P = 0.0399), rs6843722 (empiric P = 0.0229) and rs6850524 (empiric P = 0.00899) and between fibrosis score and rs1554483 (empiric P = 0.02697), rs6843722 (empiric P = 0.01898) and rs4864548 (empiric P = 0.02697). Test of haplotypic association showed that CLOCK gene variant haplotypes frequencies in NAFLD individuals significantly differed from those in controls (empiric P = 0.0097).
  
  
  CONCLUSIONS
  Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes in susceptibility to NAFLD and disease severity.
authors: Instituto de Investigaciones Medicas, A. Lanari. Universidad de Buenos Aires, CONICET, Combatiente de Malvinas 3150, 1427- Ciudad Autonoma de Buenos Aires, Argentina. ssookoian@intramed.net
authors: Silvia
authors: S
authors: Sookoian
authors: Gustavo
authors: G
authors: Castaño
authors: Carolina
authors: C
authors: Gemma
authors: Tomas-Fernández
authors: TF
authors: Gianotti
authors: Carlos-Jose
authors: CJ
authors: Pirola
mesh_terms: D001706:Biopsy; D056926:CLOCK Proteins; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012720:Severity of Illness Index; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D015534:Trans-Activators; D056926:CLOCK Proteins; C538943:CLOCK protein, human
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