Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease
Common genetic variations in CLOCK transcription factor are associated with nonalcoholic fatty liver disease
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DOI：
10.3748/wjg.v13.i31.4242
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发表时间：
2007-08-21
影响因子：
4.3
通讯作者：
Pirola, Carlos Jose
中科院分区：
文献类型：
--
作者：
Sookoian, Silvia;Castano, Gustavo;Pirola, Carlos Jose
目的：为探讨CLOCK转录因子基因变异及其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，对136例NAFLD患者和64例健康人进行了研究。对91例患者进行了肝活检。6个标签SNP显示次要等位基因频率> 10%对4号染色体117 kb的115个多态位点（rs 1554483 C/G; rs 11932595 A/G; rs 4580704 C/G; rs6843722 A/C; rs6850524 C/G和rs 4864548 A/G）进行基因分型（r（2）> 0.8）。rs 11932595和rs6843722与NAFLD显著相关（经验P值分别为0.0449和0.023）。在NAFLD的临床或组织学谱和rs 1554483之间也观察到显著的关联（经验P = 0.0399），rs6843722（经验P = 0.0229）和rs6850524（经验P = 0.00899）以及纤维化评分与rs 1554483（经验P = 0.02697）、rs6843722（经验P = 0.01898）和rs 4864548（经验P = 0.02697）之间的差异。单倍型关联检验显示，CLOCK基因变异单倍型频率在NAFLD个体中与对照组有显著性差异（经验P = 0.0097）。结论：CLOCK基因多态性及其单倍型可能与NAFLD的易感性和疾病严重程度有关。(c)2007年WJG。All rights reserved.
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. (c) 2007 WJG. All rights reserved.