Sookoian Silvia, Castaño Gustavo, Gemma Carolina, Gianotti Tomas-Fernández, Pirola Carlos-Jose
Instituto de Investigaciones Medicas, A. Lanari. Universidad de Buenos Aires, CONICET, Combatiente de Malvinas 3150, 1427- Ciudad Autonoma de Buenos Aires, Argentina.
World J Gastroenterol. 2007 Aug 21;13(31):4242-8. doi: 10.3748/wjg.v13.i31.4242.
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.
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.
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).
Our study suggests a potential role of the CLOCK polymorphisms and their haplotypes in susceptibility to NAFLD and disease severity.
研究生物钟转录因子的基因变异和衍生单倍型在非酒精性脂肪性肝病（NAFLD）中的作用及其与疾病严重程度的关系。
共研究了136例NAFLD患者和64例健康个体。91例患者进行了肝活检。对6个标签单核苷酸多态性（SNP）进行基因分型，这些SNP的次要等位基因频率>10%（rs1554483 C/G；rs11932595 A/G；rs4580704 C/G；rs6843722 A/C；rs6850524 C/G和rs4864548 A/G），覆盖4号染色体117 kb，代表115个多态性位点（r²>0.8）。
rs11932595和rs6843722与NAFLD显著相关（经验P值分别为0.0449和0.023）。在NAFLD的临床或组织学谱与rs1554483（经验P值=0.0399）、rs6843722（经验P值=0.0229）和rs6850524（经验P值=0.00899）之间，以及纤维化评分与rs1554483（经验P值=0.02697）、rs6843722（经验P值=0.01898）和rs4864548（经验P值=0.02697）之间也观察到显著关联。单倍型关联检验表明，NAFLD个体中生物钟基因变异单倍型频率与对照组显著不同（经验P值=0.0097）。
我们的研究表明生物钟多态性及其单倍型在NAFLD易感性和疾病严重程度中可能起作用。
