PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty liver in middle-aged and older Chinese population
PPARG gene Pro12Ala variant contributes to the development of non-alcoholic fatty liver in middle-aged and older Chinese population
复制标题
PPARG基因Pro12Ala变异导致中国中老年人非酒精性脂肪肝的发生
DOI：
10.1016/j.mce.2011.09.001
复制
发表时间：
2012-01-02
影响因子：
4.1
通讯作者：
Hu, Renming
中科院分区：
文献类型：
--
作者：
Yang, Zhen;Wen, Jie;Hu, Renming
氧化应激被认为是非酒精性脂肪性肝病(NAFLD)的发病原因之一。PPAR-γ杂合子小鼠和PPARG的Pro12Ala(C/G)多态小鼠对氧化应激的抵抗力增强。吸烟会增加活性氧的产生，在营养过剩的情况下会加速氧化应激。为探讨C/G基因多态性是否单独或联合吸烟对非酒精性脂肪肝的发病有促进作用，对903名中国受试者进行了病例对照研究。在研究人群中，436例经B超证实的NAFLD患者(318例脂肪肝I度，90例脂肪肝II度，28例脂肪肝III度)和467名对照组用TaqMan等位基因辨别法进行了基因分型。在调整混杂因素后，C/C基因型与非酒精性脂肪肝显著相关(OR=1.87，95%CI1.13~2.85，p=0.009)，吸烟也是非酒精性脂肪肝的独立危险因素(OR=1.69，95%CI1.18~2.43，p=0.025)。此外，我们发现了可能的协同效应，在调整混杂因素(p<；0.001)后，在多因素Logistic分析中，高风险组(C/C基因型吸烟者)患非酒精性脂肪肝的风险是低风险组(C/G基因型吸烟者)的3.75倍，但没有发现偏离可加性的情况。结果表明，C/C基因型和吸烟是NAFLD的显著独立危险因素。基因与吸烟可能的协同作用可能通过加重氧化应激而促进NAFLD的发生发展，支持氧化应激参与NAFLD发生的假说。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Oxidative stress has been suggested to contribute to the development of non-alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which could accelerates oxidative stress under overnutrition. To explore whether the C/G polymorphism, alone or in combination with smoking, may promote the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among the study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis I degrees, 90 with steatosis hepatis II degrees and 28 with steatosis hepatis III degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. After adjusting for confounders, the C/C genotype significantly associated with NAFLD (OR = 1.87, 95%CI 1.13-2.85, p = 0.009); smoking was also an independent risk factor for NAFLD (OR = 1.69, 95%CI 1.18-2.43, p = 0.025). In addition, we found possible synergistic effects, the higher risk group (smokers with the C/C genotype) showed 3.75 times higher risk of NAFLD than the low-risk group (non-smokers with C/G genotype) in a multiple logistic analysis after adjusting for the confounders (p < 0.001), but no departure from additivity was found. Our results indicated that the C/C genotype and smoking were significant independent risk factors for NAFLD. The possible synergistic effects of genotype and smoking may promote the development of NAFLD by aggravating oxidative stress, which supports the hypothesis that oxidative stress contributes to the development of NAFLD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.