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 pat...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.展开更多
基金Supported by Grant B119 (Universidad de Buenos Aires), PICT 25920 (Agencia Nacional de Promoción Científi ca y Tecnológica) and PIP 5195 (Consejo Nacional de Investigaciones Científicas y Técnicas). SS, CG and CJP belong to Consejo Nacional de Investigaciones Científi cas y Técnicas
文摘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.
