Polymorphisms of tumor necrosis factor alpha gene and coronary heart disease in a Chinese Han population: Interaction with cigarette smoking

Introduction: Tumor necrosis factor alpha (TNF-alpha) is a primary pro-inflammatory cytokines and has been implicated in cardiovascular disease pathogenesis. Relationship between polymorphisms in TNF-alpha gene and coronary heart disease (CHD) has been reported, but remains a controversial one. Materials and Methods: A single nucleotide polymorphism (SNP) discovery in a total of 4739 base pairs in the promoter region, exon region and exon/intron boarding region of TNF-alpha gene in randomly selected 48 patients by direct sequencing was conducted. Four SNPs (-806C>T, -308G>A, -238G>A, and +467G>A) out of seven polymorphisms identified were further investigated for associations in 804 CHD patients (of which 504 patients with Myocardial infarction (MI)) and 905 age- and gender-matched controls. Results: No main effects of loci and haplotypes reached statistical significance in the total sample. However, a significant gene-smoking interaction was observed. In nonsmokers, compared with individuals of G/G genotype, individuals carrying the A allele of the -238G>A polymorphism showed a lower risk of developing CHD (odds ratio 0.48, 95%CI 0.24-0.94, P = 0.033), and an even lower risk of developing MI (odds ratio 0.36, 95%CI 0.15-0.88, P = 0.026). Haplotype analysis confirmed the results of individual polymorphism analyses. In addition, the -806C>T polymorphism was found to be associated with MI in smokers (P = 0.039). Conclusions: This study identified a significant interaction between TNF-alpha gene and smoking status. Both single locus and haplotype analyses indicated that A allele of the -238G>A polymorphism decreased the risk of CHD among nonsmokers in Chinese Han population. (C) 2008 Elsevier Ltd. All rights reserved.