Association of TNF-alpha-238G/A and 308 G/A gene polymorphisms with pulmonary tuberculosis among patients with coal worker's pneumoconiosis.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) may play an important role in host's immune response to mycobacterium tuberculosis (M. tuberculosis) infection. This study was to investigate the association of TNF-alpha gene polymorphism with pulmonary tuberculosis (TB) among patients with coal worker's pneumoconiosis (CWP).


METHODS
A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-alpha gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP). Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher's exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplicative model with combined OR. All data were analyzed using SAS version 8.2 software.


RESULTS
No significant difference in frequency of the TNF-alpha-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls (chi2 = 5.44, P = 0.07). But difference in frequency of the TNF-alpha-308 A allele was identified between them (chi2 = 5.14, P = 0.02). No significant difference in frequencies of the TNF-alpha-238 genotype and allele (P = 0.23 and P = 0.09, respectively) was found between cases and controls either, with combined (GG and AA) OR of 3.96 (95% confidence interval of 1.30-12.09) at the -308 locus of the TNF-alpha gene, as compared to combination of the TNF-alpha-238 GG and TNF-alpha-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-alpha-238 GG and TNF-alpha-308 GA genotypes was 1.98 (95% CI of 1.06-3.71) for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-alpha-308 GG genotype and body mass index (OR = 4.92), as well as an interaction between the TNF-alpha-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-alpha-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated.


CONCLUSIONS
TNF-alpha-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-alpha-238 A allele was otherwise.
Fan
Hong-Min
HM
School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Wang
Zhuo
Z
Feng
Fu-Min
FM
Zhang
Kong-Lai
KL
Yuan
Ju-Xiang
JX
Sui
Hong
H
Qiu
Hong-Yan
HY
Liu
Li-Hua
LH
Deng
Xiao-Juan
XJ
Ren
Jing-Xue
JX
D000368:Aged; D000369:Aged, 80 and over; D055008:Anthracosis / Q000150:complications*; D016022:Case-Control Studies; D004781:Environmental Exposure; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha