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. 2007 Aug 21;13(31):4242-8.
doi: 10.3748/wjg.v13.i31.4242.

Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease

Silvia Sookoian  1 , Gustavo Castaño, Carolina Gemma, Tomas-Fernández Gianotti, Carlos-Jose Pirola
Affiliations

Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease

Silvia Sookoian et al. World J Gastroenterol. .

Abstract

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.

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).

Conclusion: Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes in susceptibility to NAFLD and disease severity.

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Figures

Figure 1
Figure 1
Linkage disequilibrium plot across the CLOCK gene. The horizontal white line depicts the 117-kb DNA segment of chromosome 4q12 analyzed in our sample. The 6 tagSNPs locations are indicated by hatch marks. A linkage disequilibrium plot is depicted in the bottom part of the figure. Each diamond represents the magnitude of LD for a single pair of markers, with colors indicating strong LD (black, r2 = 1.0) and no LD (white, r2 = 0) as the extremes (different gray tones indicate intermediate LD). Numbers inside the diamonds stand for D’ values.
See this image and copyright information in PMC

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