Cao Ming-bo, Yang Yu-xiu, Dong Lei
Department of Gastroenterology, Henan Provincial Peoples Hospital, Zhengzhou 450000, China.
Zhonghua Gan Zang Bing Za Zhi. 2010 Oct;18(10):773-7. doi: 10.3760/cma.j.issn.1007-3418.2010.10.012.
To study the relationship between COX-2 gene and hereditariness to Nonalcoholic fatty liver disease by detecting single nucleotide polymorphisms in the promoter of COX-2 gene.
Genotypes of 200 case patients with NAFLD and 206 control subjects were examined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). The DNA samples were extracted from the peripheral blood of all subjects.
Two SNPs, -1195G more than A and -765 G more than C, were identified with frequencies of variant alleles 54% and 5% in patients with NAFLD and 48% and 2% in control, respectively. A case-control analysis revealed a 1.13-fold (95% CI = 1.01-2.46) and a 2.35-fold (95% CI = 1.17-3.65) excess risk of developing NAFLD for -1195AA or -765CG genotype carriers compared with noncarriers. Compared with G-1195-G-765 containing haplotype, a greater risk of developing NAFLD was observed for A-1195-G-765 (OR =1.42; 95% CI =1.11-1.63) and A-1195-C-765 (OR = 4.24; 95% CI =1.72-14.22) containing haplotypes. A greater risk of developing NAFLD was observed for A-1195 and C-765 containing haplotype compared with other haplotype, suggesting an interaction between the -1195A and -765C in the context of haplotype.
These findings suggest that genetic variants in the COX-2 promoter may play an important role in mediating susceptibility to developing NAFLD in a Chinese population. -1195G more than A and -765G more than C in promoter region of Cyclooxygenase-2 gene, whose single nucleotide polymorphisms are related with development of NAFLD, are the significance factors of the susceptibility of NAFLD.
通过检测环氧化酶-2（COX-2）基因启动子区的单核苷酸多态性，研究COX-2基因与非酒精性脂肪性肝病遗传易感性之间的关系。
采用基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）方法检测200例非酒精性脂肪性肝病患者和206例对照者的基因型。所有受试者的DNA样本均从外周血中提取。
在非酒精性脂肪性肝病患者中，发现两个单核苷酸多态性位点，即-1195G＞A和-765G＞C，其变异等位基因频率分别为54%和5%；在对照组中，变异等位基因频率分别为48%和2%。病例对照分析显示，与非携带者相比，-1195AA或-765CG基因型携带者发生非酒精性脂肪性肝病的风险分别增加1.13倍（95%可信区间=1.01-2.46）和2.35倍（95%可信区间=1.17-3.65）。与包含G-1195-G-765的单倍型相比，包含A-1195-G-765（比值比=1.42；95%可信区间=1.11-1.63）和A-1195-C-765（比值比=4.24；95%可信区间=1.72-14.22）的单倍型发生非酒精性脂肪性肝病的风险更高。与其他单倍型相比，包含A-1195和C-765的单倍型发生非酒精性脂肪性肝病的风险更高，提示在单倍型背景下，-1195A和-765C之间存在相互作用。
这些发现提示，COX-2启动子区的基因变异可能在中国人群非酒精性脂肪性肝病易感性的介导中起重要作用。环氧化酶-2基因启动子区的-1195G＞A和-765G＞C单核苷酸多态性与非酒精性脂肪性肝病的发生有关，是其易感性的重要因素。
