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。
Objective To investigate the association of 5 s ingle nucleot ide polymorph isms and their haplotypes in the promoter of tumor necrosis factor (TNF ) genewith coronary artery disease (CAD) in Shangha iH an population. Methods The genotypes ofT 1031C, C 863A, C 857T, G 308A and G 238A polymorphismswere analysed by mass spectrometry in 438 patients w ith CAD and 330 healthy controls, and concentrat ions of blood glucose and blood lipid were measured. Results Therewere significant differences in genotype and allele frequency of C 857T polymorphism between CAD group and control group (P < 0. 05). Patients carrying - 857C allelewere associated with 1. 45 fold higher odds ofCAD compared to T allele carriers ( 95% CI, 1. 092- 1. 927). In patients w ith CAD, serum levels of tota l cholesterol and low density lipoprotein cholesterol ofC /C genotype and C/T genotype carriers were s ign ificantly higher than those ofT /T carriers (P < 0. 05). There were s ignificant differences in allele frequency ofG 308A polymorphism between two groups (P < 0. 05). Patients carrying - 308A allele were associated w ith 1. 43 fold h igher odds of CAD compared to noncarriers ( 95% CI, 1. 055- 1. 949). H aplotype analys is indicated that the frequencies of haplotype CCCGA and TCCAG were s ign ificantly h igher 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 s ignificantly lower in CAD group than in controls, which was significantly assoc iated with a decreased risk ofCAD (OR, 0. 57; 95%CI, 0. 415- 0. 784; P < 0. 01). Conclusion Polymorphisms in the promoter of ofTNF genem ight be associated with the occurrence of CAD in Shanghai H an population.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2011年第5期592-597,共6页
Journal of Shanghai Jiao tong University:Medical Science
基金
国家自然科学基金(81070177)
上海市科学技术发展基金(08411963500)~~
关键词
肿瘤坏死因子
单核苷酸多态
单倍型
冠心病
tumor necrosis factor-α
single nucleotide polymorphism
haplotype
coronary artery disease
