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