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

作     者：Silvia Sookoian Gustavo Castao Carolina Gemma Tomas Fernández Gianotti Carlos Jose Pirola 

作者机构：Instituto de Investigaciones Medicas A. Lanari. Universidad de Buenos Aires CONICET Combatiente de Malvinas 3150 1427-Ciudad Autonoma de Buenos Aires Argentina Consejo de Investigación GCBA Buenos Aires Argentina Consejo de Investigación GCBA Buenos Aires Argentina Instituto de Investigaciones Medicas A. Lanari. Universidad de Buenos Aires CONICET Combatiente de Malvinas 3150 1427-Ciudad Autonoma de Buenos Aires Argentina 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2007年第13卷第31期

页      面：4242-4248页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

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 

主　　题：生理节奏 蛋白质 基因变异 肝疾病 

摘      要：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 (r2 0.8) were genotyped. RESULTS: rs11932595 and rs6843722 showed signifi cant 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.