This meta-analysis, robustly investigated associations between TNF-α, IL-1 or IL-6 polymorphisms and the risk of asthma. The quantitative analyses results demonstrated that TNF-α -238 G/A, TNF-α -308 G/A and IL-6 -174 G/C polymorphisms were all significantly associated with the risk of asthma. Nevertheless, we did not detect such positive association for the IL-1B − 511 C/T polymorphism.
The following points should be considered when interpreting our findings. First, based on findings of previous experimental studies, it is thought that investigated TNF-α, IL-1 or IL-6 polymorphisms may alter mRNA expression level of TNF-α, IL-1 and IL-6, generate a imbalance status between Th1 and Th2 related immune responses, and ultimately influence the risk of asthma [12–13]. Therefore, considering the functional significances of investigated polymorphisms, our integrated quantitative analyses may be still statistically insufficient to detect the real association between IL-1B − 511 C/T polymorphism and the risk of asthma, and future studies with larger sample sizes are still warranted to confirm our findings. Second, we wish to study all polymorphic loci of TNF-α, IL-1 and IL-6. Nevertheless, our literature searching did not reveal sufficient eligible literatures to support integrated quantitative analyses for other polymorphic loci of these cytokines, so we only explored associations with the risk of asthma for several most common TNF-α, IL-1 and IL-6 polymorphisms. Third, it is also worth noting that polymorphisms in other Th1-related cytokines such as IL-8, IL-12, IL-23 and IL-31 could not be investigated in this meta-analysis because only a few previous publications tried to elucidate the roles of these polymorphisms in asthma, and therefore, we could not find sufficient literatures to warrant quantitative analyses.
As with all meta-analyses, the present study has several major limitations. Firstly, our quantitative analyses results were only based on unadjusted integrating of previous literatures. Without access to raw data of eligible studies, we can only estimate associations based on re-calculations of raw genotypic or allelic frequencies, but we have to admit that lack of further adjustment for baseline characteristics such as age and sex may certainly influence reliability of our findings [14]. Secondly, environmental factors such as hygiene status or air quality may also influence associations between TNF-α, IL-1 or IL-6 polymorphisms and the risk of asthma. However, most of previous literatures did not report environmental factors, so it is impossible for us to explore genetic-environmental interactions in a meta-analysis based on previous literatures [15]. Thirdly, we did not search for 'grey literatures' that were not formally published in peer-reviewed scientific journals because these literatures are always incomplete and it is impossible for us to assess their quality using the NOS scale. Nevertheless, since we did not consider 'grey literatures' for quantitative analyses, despite that funnel plots were found to be overall symmetrical, we acknowledged that publication biases still may impact reliability of our integrated findings [16].