摘要
目的:探讨中国汉族人肿瘤坏死因子-α(tumor necrosis fac- tor-α,TNF-α)基因启动子单核苷酸多态性与乙型肝炎病毒(hepatitis B virus,HBV)感染结果之间的关系. 方法:慢性乙型肝炎患者131例,HBV感染自愈者165组. 应用聚合酶链反应-限制性片段长度多态性分析方法,检测HBV感染自愈者和慢性乙型肝炎患者TNF-α基因启动子-238G/A,-308G/A,-857C/T和-863C/A单核苷酸多态性位点基因型. 结果:对慢性乙型肝炎组和HBV感染自愈组人群TNF-α基因启动子区域的-238G/A,-308G/A,-857C/T和-863C/A 4个SNP位点进行基因型分析,共发现12种启动子基因型,以GG·GG·CC·CC,GG·GG·CC·CA,GG·GG·CT·CC和GG·GA·CC·CC基因型多见,约占85%.通过对慢性乙型肝炎患者和HBV感染自愈者TNF-α基因启动子4个位点基因型联合分析发现,GG·GG·CC·CC, GG·GG·CC·CA和GG·GA·CC·CC基因型在慢性乙型肝炎组和HBV感染自愈组分布差异有显著性,其中携带GG·GG·CC·CC基因型的个体患慢性乙型肝炎的机会比(odds ratio,OR)为2.15,95%可信区间为1.34-3.45;而携带GG·GG·CC·CA或GG·GA·CC·CC基因型的个体患慢性乙型肝炎的OR分别为0.48(95%可信区间为0.27-0.86)和0.35(95%可信区间为0.14-0.89).HBV感染的清除可能与GG·GG·CC·CA(X2=6.14,P=0.013<0.05) 和/或GG·GA·CC·CC(X2=5.18,P=0.023<0.05)基因型有关.进一步对各位点单核苷酸多态性分析发现, 慢性乙型肝炎患者和HBV感染自愈者TNF-α基因启动子-238G/A、-857C/T位点基因型分布频率差异无显著性,而-308G/A,-863C/A位点基因型分布频率差异有显著性(-308G/A位点,)X2=6.53,P=0.011<0.05,OR=3.05; -863C/A位点,X2=4.33,P=0.037<0.05,OR=1.69). 结论:TNF-α基因启动子-308G/A、-863C/A位点多态性与中国汉族人HBV感染后的结果有关,其中TNF-α-308G/A 和/或-863C/A位点A等位基因的存在可能有利于HBV感染的清除.
AIM: To investigate the polymorphism of tumor necrosis factor-α (TNF-α) gene promoters in Chinese Han people, and to clarify whether such polymorphism was associated with the outcome of hepatitis B virus infection. METHODS: After the process of extracting genomic DNA from blood in 165 subjects who spontaneously recovered (SR) and 131 patients with chronic hepatitis B (CHB), four single nucleotide polymorphism (SNP) sites in TNF-α gene promoter marked as -238G/A, -308G/A, -857C/T and -863C/A were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. RESULTS: Twelve different promoter genotypes were detected from all of 296 research subjects, and GG·GG·CC·CC, GG·GG·CC·CA, GG·GG·CT·CC, GG·GA·CC·CC genotypes accounted for about 85% of genotypes in these subjects. By analyzing the four promoter genotypes of TNF-α, the results showed that there were significant differences in the frequencies of GG·GG·CC·CC, GG·GG·CC·CA and GG·GA·CC· CC genotypes in TNF-α gene promoter between CHB and SR, GG·GG·CC·CC genotype carriers were at increased risk of CHB with an odds ratio of 2.15 (95% CI 1.34-3.45); While GG·GG·CC·CA and GG·GA·CC·CC genotypes carriers were at increased risk of CHB with an odds ratio of 0.48 (95% CI 0.27-0.86) and 0.35 (95% CI 0.14-0.89), respectively. GG·GG·CC·CA and GG·GA·CC·CC genotypes were strongly associated with the resolution of HBV infection (X2=6.14, P =0.013<0.05; X2=5.18, P =0.023<0.05, respectively). Single site analysis also revealed that TNF-α gene -308G/A and -863C/A SIMP sites were associated with persistent HBV infection in Chinese Han people (-308G/ A site, X2=6.53, p=0.011<0.05, OR=3.21; -863C/A site, X2=4.33, P=0.037<0.05, OR=1.69, respectively). CONCLUSION: There is an association between polymorphisms of the promoter region -308G/A and -863C/A of TNF-α and the resolution of HBV infection. The presence of the -308A allele (TNF-α-308GA) and/or -863A allele (TNF-α-863CA or AA) may be resistant to
出处
《世界华人消化杂志》
CAS
2004年第9期2086-2090,共5页
World Chinese Journal of Digestology
