肿瘤坏死因子-α基因多态性与非酒精性脂肪性肝病的关系  

Association of nonalcoholic fatty liver disease with tumor necrosis factor-α gene polymorphisms

作　　者：周永健[1] 李瑜元[1] 聂玉强[1] 黄健[1] 石胜利[1] 李永强[1] 杜艳蕾[1] 

机构地区：[1]广州市第一人民医院消化内科,510180

出　　处：《中华消化杂志》2006年第5期311-314,共4页Chinese Journal of Digestion

基　　金：广州市卫生局重点项目(2004Z001)

摘　　要：目的研究肿瘤坏死因子-α(TNF-α)基因-308位点及-238位点多态性在非酒精性脂肪性肝病(NAFLD)患者中的分布,及其在胰岛素抵抗(IR)和 NAFLD 发病中的地位。方法运用聚合酶链反应-限制性片段长度多态性检测117例 NAFLD 患者 TNF-α基因—308位点及—238位点多态性,其中伴肥胖者60例,非肥胖者57例,同时测定患者空腹血清胰岛素(FINS)及空腹血糖,通过体内平衡代谢指数(HOMA)评估 IR,并与120名健康者对照。结果 NAFLD 患者与正常对照组 TNF-α基因-238位点基因多态性分布差异有统计学意义(29.9%比15.8%,P<0.05),而—308位点差异无统计学意义(P>0.05)。NAFLD 患者血清 HOMA-IR、TNF-α明显高于对照者[2.50±0.68比1.16±0.68,(10.54±3.19)ng/L 比(4.54±3.10)ng/L,P<0.01]。FINS、HOMA-IR 在 TNF-α基因-238位点基因变异组明显高于正常基因型组(P<0.05),但在—308位点变异组差异无统计学意义(P>0.05)。NAFLD 患者中无论肥胖或非肥胖患者均较正常对照人群在 TNF-α基因-238位点多态性分布及HOMA-IR、TNF-α差异有统计学意义(P<0.05)。肥胖及非肥胖的 NAFLD 患者之间 HOMA-IR、TNF-α差异无统计学意义(P>0.05)。结论 NAFLD 患者 IR 与其体重关系不显著,非肥胖 NAFLD患者同样有 IR 发生。TNFα基因-238位点 G/A 变异与 IR、NAFLD 易感性相关,TNFα基因-308位点 G/A 的突变与 IR 易感性不相关。NAFLD 发病与 IR、TNF-α密切相关。Objective To investigate the prevalence of tumor necrosis factor-α（TNF-α） promoter polyrnorphisms （at position -308 or -238） in patients with nonalcoholic fatty liver disease（NAFLD）, and to explore the relationship between TNF-α promoter polymorphisrns and obesity and the insulin resistance （IR） in those patients. Methods Metabolic variables were measured in 117 patients with NAFLD, among them 60 were obesity and 57 were non-obesity. Genotype of TNF-α promoter were determined by PCR-RFLP. Plasma TNF-α level was measured by ELISA. Indexes of IR and insulin secretion were determined using the homeostasis model assessment method. One hundred and twenty normal subjects who were matched for age and sex served as control. Results The G→A mutation of the -238 TNF-α polymorphism was significantly higher in patients with NAFLD versus controls （29. 9% vs. 15. 8%, P 〈 0.05）, while the difference of TNF-α -308 polymorphism was no statistically significant in these two groups. Plasma TNF-α level and fasting insulin were significantly higher in GA group than that in GG group in NAFLD patients. IR and average insulin concentration were independently associated with NAFLD. The exclusion of overweight and obese subjects did not change the results. Conclusion NAFLD is associated with insulin resistance and TNF-α polymorphisms even in lean subjects with normal glucose tolerance. TNF-α -238C→A polymorphism is associated with NAFLD. A allele might involved in IR by increasing the release of TNF-α levels, which leads to NAFLD.

关 键 词：非酒精性脂肪肝 肿瘤坏死因子 基因多态性 

分 类 号：R575.5[医药卫生—消化系统]