上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (5): 592-.doi: 10.3969/j.issn.1674-8115.2011.05.015

• 论著（临床研究） • 上一篇    下一篇

肿瘤坏死因子α基因与上海地区汉族人群冠心病发病风险的关系

刘 艳, 陆 林, 吴志俊, 陈秋静, 沈卫峰, 金 玮   

  1. 上海交通大学 医学院附属瑞金医院心内科 |上海交通大学心血管病研究所, 上海 200025
  • 出版日期:2011-05-28 发布日期:2011-05-27
  • 通讯作者: 金 玮, 电子信箱: jinwei_ivy@126.com。
  • 作者简介:刘 艳（1970—）, 女, 副主任医师, 博士, 硕士生导师；电子信箱: liuyan_ivy@126.com。
  • 基金资助:

    国家自然科学基金（81070177）；上海市科学技术发展基金（08411963500）

Relationship between tumor necrosis factor-alpha gene and risk of coronary artery disease in Shanghai Han population

LIU Yan, LU Lin, WU Zhi-jun, CHEN Qiu-jing, SHEN Wei-feng, JIN Wei   

  1. Department of Cardiology, Ruijin Hospital, Institute of Cardiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2011-05-28 Published:2011-05-27
  • Supported by:

    National Natural Science Foundation of China, 81070177；Shanghai Science and Technology Development Foundation, 08411963500

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摘要：

目的 研究肿瘤坏死因子α（TNF-α）基因启动子区域5种单核苷酸多态及其构成单倍型与上海地区汉族人群冠心病（CAD）发病的相关性。方法 采用质谱检测方法，对438例CAD患者和330名健康对照者的TNF-α基因启动子区域的T-1031C、C-863A、C-857T、G-308A和G-238A多态进行基因分型;并检测受试者的血糖和血脂浓度。结果 C-857T多态基因型分布及其等位基因频率在CAD组和对照组间比较差异有统计学意义（P<0.05），-857C等位基因携带者的CAD发病风险是T携带者的1.45倍（95%CI=1.092~1.927）。CAD患者中，C/C基因型和C/T基因型的血清总胆固醇浓度和低密度脂蛋白胆固醇浓度明显高于其T/T基因型携带者，差异有统计学意义（P<0.05）。两组间G-308A多态等位基因频率比较差异也有统计学意义（P<0.05），-308A等位基因携带者的CAD风险是非携带者的1.43倍（95%CI=1.055~1.949）。单倍型分析提示，单倍型CCCGA和TCCAG频率在CAD组明显升高，与对照组相比差异有统计学意义（P<0.05和P<0.01），其携带者的CAD风险分别是非携带者的2.96和1.67倍（95%CI分别为1.176~7.430和1.166~2.379）；而单倍型TCTGG在对照组中明显增加，可降低CAD的发病风险（OR=0.57，95%CI=0.415~0.784，P<0.01）。结论 TNF-α基因启动子区域多态可能与上海地区汉族人群CAD的发病相关。

关键词: 肿瘤坏死因子α, 单核苷酸多态, 单倍型, 冠心病

Abstract:

Objective To investigate the association of 5 single nucleotide polymorphisms and their haplotypes in the promoter of tumor necrosis factor-α (TNF-α) gene with coronary artery disease (CAD) in Shanghai Han population. Methods The genotypes of T-1031C, C-863A, C-857T, G-308A and G-238A polymorphisms were analysed by mass spectrometry in 438 patients with CAD and 330 healthy controls, and concentrations of blood glucose and blood lipid were measured. Results There were significant differences in genotype and allele frequency of C-857T polymorphism between CAD group and control group (P<0.05). Patients carrying -857C allele were associated with 1.45-fold higher odds of CAD compared to T allele carriers (95%CI, 1.092-1.927). In patients with CAD, serum levels of total cholesterol and lowdensity lipoprotein cholesterol of C/C genotype and C/T genotype carriers were significantly higher than those of T/T carriers (P<0.05). There were significant differences in allele frequency of G-308A polymorphism between two groups (P<0.05). Patients carrying -308A allele were associated with 1.43-fold higher odds of CAD compared to noncarriers (95%CI, 1.055-1.949). Haplotype analysis indicated that the frequencies of haplotype CCCGA and TCCAG were significantly higher in CAD group than in control group (P<0.05 and P<0.01), and the risks of suffering from CAD were 2.96 fold and 1.67 fold for homozygous carriers of haplotype CCCGA and TCCAG compared to noncarriers (95%CI, 1.176-7.430 and 1.166-2.379). In comparison, the frequency of haplotype TCTGG was significantly lower in CAD group than in controls, which was significantly associated with a decreased risk of CAD (OR, 0.57; 95%CI, 0.415-0.784; P<0.01). Conclusion Polymorphisms in the promoter of of TNF-α gene might be associated with the occurrence of CAD in Shanghai Han population.

Key words: tumor necrosis factor-α, single nucleotide polymorphism, haplotype, coronary artery disease