Polymorphisms of STAT-6, STAT-4 and IFN-gamma genes and the risk of asthma in Chinese population.
BACKGROUND
Asthma is a complex disease resulting from multiple gene-gene and gene-environment interactions. Study on gene-gene interactions could provide insight into the pathophysiologic mechanisms of the disease.


OBJECTIVE
We investigated the single nucleotide polymorphisms and interactions among three different loci in three candidate genes (STAT-6 G2964A, STAT-4 T90089C and IFN-gamma T874A) in 95 Chinese asthmatic subjects and 95 matched controls to determine the possible associations with asthma.


METHODS
Genotyping of the gene polymorphisms was performed by means of PCR-SSCP analysis. Genotype-phenotype associations were examined in dominant and recessive genetic models using logistic regression. The method of multifactor dimensionality reduction was used to analyze gene-gene interactions.


RESULTS
No statistically significant difference was found in the distribution of the STAT-6 G2964A polymorphisms between asthmatic patients and controls in this case-control study. The STAT-4 T90089C polymorphisms were significantly associated with asthma in the dominant model (p=0.007). As for the IFN-gamma T874A, the significant associations were found in both dominant model (p=0.004) and recessive model (p=0.006). A significant gene-gene interaction was found among STAT-6, STAT-4 and IFN-gamma on the risk of asthma. In the best 3-locus model, the odds ratio for the high-risk to the low-risk group was 6.9 (95% CI, 3.5-13.7; p<0.0001).


CONCLUSIONS
Our findings suggest that STAT-4 T90089C and IFN-gamma T874A polymorphisms might be the genetic factors for the risk of asthma in the Chinese population. In addition, the significant interactions among STAT-6 G2964A, STAT-4 T90089C and IFN-gamma T874A may increase an individual's susceptibility and contribute to the pathogenesis of asthma.
Li
Yafei
Y
Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, PR China. yafeilye@yahoo.com.cn
Wu
Bo
B
Xiong
Hongyan
H
Zhu
Caizhong
C
Zhang
Lu
L
D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D050797:STAT4 Transcription Factor / Q000235:genetics*; D050800:STAT6 Transcription Factor / Q000235:genetics*
D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D007371:Interferon-gamma