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

To investigate the role of gene variants and derived haplotypes of the CLOCK transcription factor in nonalcoholic fatty liver disease （NAFID） 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 （P 〉 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 insusceptibility to NAFLD and disease severity.

Role of ABCC2 common variants in intrahepatic cholestasis of pregnancy

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP), a disorder that adversely affects maternal wellbeing and fetal outcome, is unclear. However, multiple factors probably interact along with a genetic predisposition. We would like to add some comments on a paper recently published concerning the role of ABCB11 and ABCC2 polymorphisms in both ICP and contraceptive-induced cholestasis, especially in the light of our recently published findings about a positive association between ICP and ABCC2 common variants.