Involvement of TNFalpha -308A promoter polymorphism in the development of asthma in children infected with Chlamydophila pneumoniae.
ABSTRACT Several data indicate a connection between Chlamydophila pneumoniae infection and asthma. Although C. pneumoniae is a common cause of infection, not all infected patients develop asthma. This suggests that certain individuals may be genetically predisposed to the chronic effects of C. pneumoniae infection on airway functions. We investigated the possible modifying effect of different polymorphisms on C. pneumoniae infection and on the susceptibility to asthma in 318 children, among those 144 had asthma and 174 had no asthmatic symptoms. C. pneumoniae-specific antibodies were measured by ELISA. Tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated on activation normal T cell expressed and secreted) genotypes were determined by PCR-restriction fragment length polymorphism (RFLP). There were no significant differences in the percentage of children positive for C. pneumoniae-specific antibodies between cases and controls. None of the genotypes was associated with altered susceptibility to C. pneumoniae infection. Among asthmatic children carrying the TNFalpha -308A allele, there were significantly more patients positive for C. pneumoniae-specific IgG, than among control children carrying the same allele (20.1% versus 9.2% of asthmatic versus control children, respectively; p = 0.002; odds ratio = 3.52 (1.52-7.53); p = 0.005). This study indicates the possible roles of polymorphisms in the immune system in the susceptibility to asthma in children infected with C. pneumoniae.
Article: The -308 G/A polymorphism in TNF-α gene is associated with asthma risk: an update by meta-analysis.[show abstract] [hide abstract]
ABSTRACT: The -308 G/A polymorphism in TNF-α gene has been extensively investigated for association to asthma; however, results of different studies have been inconsistent. The aim of this study is to comprehensively evaluate the genetic risk of -308 G/A polymorphism in TNF-α gene for asthma. A meta-analysis was carried out to analyze the association between the -308 G/A polymorphism TNF-α gene and asthma risk. A total of 4717 cases and 5012 controls in 29 case-control studies were included in this meta-analysis. The result indicated that the variant A allele carriers had a 38% increased risk of asthma, when compared with the homozygote GG (odds ratio (OR) = 1.40, 95% confidence interval (CI), 1.13-1.68 for AA + AG vs. GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with A allele carriers in Asians (OR = 1.53, 95% CI = 1.17-2.01 and P = 0.002) but not in Caucasians(OR = 1.06, 95% CI = 0.75-1.50 and P = 0.73). In the subgroup analysis by age, significant elevated risks were associated with A allele carriers in adults (OR = 1.44, 95% CI = 1.14-1.81, and P = 0.002) and children (OR = 1.37, 95% CI = 1.03-1.82, and P = 0.003). In the subgroup analysis by atopic status, significant elevated risks of asthma were associated with A allele carriers in atopic population (OR = 1.68, 95% CI = 1.34-2.10, and P < 0.00001) but not in non-atopic population (OR = 0.98, 95% CI = 0.58-1.68, and P = 0.95). Our results suggest that the TNF-α -308 G/A polymorphism contributes to susceptibility to asthma.Journal of Clinical Immunology 11/2010; 31(2):174-85. · 3.08 Impact Factor