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


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.
Hou
Liping
L
Department of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, People's Republic of China.
Huang
Jianfeng
J
Lu
Xiangfeng
X
Wang
Laiyuan
L
Fan
Zhongjie
Z
Gu
Dongfeng
D
D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003327:Coronary Disease / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha