Common Genetic Variations In Clock Transcription Factor Are Associated With Nonalcoholic Fatty Liver Disease.

SOOKOIAN S; CASTAÑO, G.; GEMMA C; FERNANDEZ GIANOTTI T; PIROLA CJ

World Journal of Gastroenterology

The WJG Press and Beijing Baishideng BioMed Technology Co., Ltd.

Lugar: Beijing, China.; Año: 2007 vol. 13 p. 4242 - 4248

1007-9327

Aim: 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. Patients & Methods: 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 (r2 >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.