北京地区慢性乙型重型肝炎患者肿瘤坏死因子基因多态性相关性分析  

Association between genetic polymorphism of tumor necrosis factor and chronic severe hepatitis B in patients

作　　者：李卓[1] 李洪权[2] 严艳[1] 刘英[2] 郝娃[1] 牛京勤[1] 殷继明[1] 李辉[2] 

机构地区：[1]首都医科大学附属北京佑安医院 北京市卫生局肝炎研究所,100069 [2]中国医学科学院基础医学研究所中国协和医科大学基础医学院流行病学教研室

出　　处：《中华医学杂志》2007年第30期2105-2108,共4页National Medical Journal of China

基　　金：北京市科委重大基金(H020920020590);北京市卫生局基金(2005-6)

摘　　要：目的探讨肿瘤坏死因子(TNF-α)基因启动子-238G/A、-308G/A、-857C/T、-863C/A 等位基因多态性和血清 TNF-α水平与慢性重型乙型肝炎的相关性。方法 2002年12月至2005年12月北京佑安医院住院慢性重型乙型肝炎患者98例,慢性乙型肝炎患者211例。采用聚合酶链反应限制性片段长度多态性分析方法检测 TNF-α启动子-238G/A、-308G/A、-857C/T、-863C/A 等位基因多态性。结果两组-863C/A、-238G/A 位点的等位基因(x^2=0.61,P=0.436;x^2=0.001,P=0.976),基因型频率比较差异无统计学意义(x^2=1.16,P=0.552;x^2=0.63,P=0.486)。两组比较 TNF-α-308 G/A 和-857C/T 等位基因差异都具有统计学意义(x^2=59.01,P=0.000;x^2=11.59,P=0.000);-308 GA 和-857 TF 基因型频率显著高于慢性乙型肝炎组(x^2=28.06,P=0.000;x^2=19.69,P=0.000),差异有统计学意义。-308 GA 与-857 TY 基因型与慢性重型乙型肝炎有显著性关联 OR=4.176;95%CI2.416-7.216;OR:6.09;95%CI 2.652-14.001。慢性重型乙型肝炎患者血清 TNF-α水平明显高于慢性肝炎患者,两组比较差异有统计学意义(t=3.951,P=0.000)。结论 TNF-α-308 GA 与-857 TF 基因型携带者感染 HBV 后可能增加成为慢性重型乙型肝炎的风险。TNF-α基因启动子区基因多态性与北京地区汉族人群中慢性重型乙型肝炎的发生可能密切相关。Objective To investigate the association between the single nucleotide polymorphisms （SNPs） of tumor necrosis factor （ TNF-α） and chronic severe hepatitis B. Methods Single nucleotide polymorphisms （SNPs）at TNF-et promoter - 238G/A, - 308G/A, - 857C/T, - 863C/A were analyzed in 98 patients with chronic severe hepatitis B and 211 patients with chronic hepatitis B in Beijing You＇an hospital; using polymerase chain reaction and restriction fragment length polymorphism （RFLP-PCR）. Results The rate of TNF-α -308 A and -857 T were34.1% vs9.5%,34.7% vs21.8% in the two gropes ;the frequencies distributions of alleles at TNF-α -308 G/A, -857C/T were significantly higher in patients with chronic severe hepatitis B than those of patients with chronic hepatitis B （ X^2 = 59.01, P = 0. 000; X^2 = 11.59, P = 0. 001 ） ; genotypes of - 308 GA, - 857 TT were significantly higher in patients with chronic severe hepatitis B than those of patients with chronic hepatitis respectively （ X^2 = 28.06, P = 0. 000 ; X^2 = 19. 69, P = 0. 000）. The frequencies of the alleles and the genotypes of TNF-α - 238G/A , - 863 C/A did not differ significantly between the chronic severe hepatitis B groups and chronic hepatitis B groups respectively（X^2 =0.61,P = 0.436;X^2 = 0.001,P = 0.976）, （X^2 = 1.16,P = 0.552;X^2 =0.63,P = 0. 486 ）. the - 308 GA, - 857 TT genotypes were associated with chronic severe hepatitis B respectively, OR reaches 4. 176 （95% CI 2. 416-7. 216） and 6. 09（95% CI 2. 652-14. 001 ）. The serum level of TNF-α were higher in patients with chronic severe hepatitis B than the patients with chronic hepatitis B （44 pg/ml± 47 pg/ml vs 10 pg/ml ± 4 pg/ml; t = 3.951, P = 0. 000）. Conclusion The genetic polymorphisms at TNF-α sites are associated with the chronic severe hepatitis B and may play an important role on the progress of HBV infection as one of the host factors.

关 键 词：肿瘤坏死因子 多态性 单核苷酸 肝炎 乙型 慢性 

分 类 号：R512.62[医药卫生—内科学]