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.

OBJECTIVES

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.