In developed countries, the prevalence of asthma has increased considerably over the past three decades. Asthma is a complex inflammatory disorder that results from interactions between more than 100 susceptibility genes and multiple environmental factors. It is, therefore, important to identify the gene variants contributing to asthma pathogenesis. Numerous studies have focused on this field, and the cytotoxic T-lymphocyte associated antigen 4 gene has been extensively studied. CTLA-4, a B7-binding protein, was initially described as a classical type I glycoprotein on the surface of activated T cells. Cumulative evidence suggested that CTLA-4 may play an important role in the pathogenesis of asthma. CTLA-4 is a powerful negative regulator of T cell activation and is associated with Th cell differentiation. Oosterwegel et al. demonstrated that CTLA-4 was a potent and critical inhibitor of Th2 cell differentiation. Expression of CTLA-4 in Th2 cells was much higher than in Th1 cells. CTLA-4 was also demonstrated to suppress the production of cytokines produced by Th2 cells. A number of studies showed that administration of CTLA-4-Ig significantly ameliorated airway hyperresponsiveness, reduced the level of eosinophils in average bronchoalveolar lavage fluid and serum IgE, as well as cytokine production in murine asthma model. Recently, Choi et al. reported that intranasal administration of Hph-1-ctCTLA-4 could significantly reduce infiltration of inflammatory cells, secretion of Th2 cytokines, serum IgE levels and AHR in a mouse model of allergic airway inflammation. Lin and co-workers demonstrated that decreased allergic inflammation by NVP-BEZ235 surfactant protein D was mediated by an increased expression of CTLA-4 in T cells. The human CTLA-4 gene is located on chromosome 2q33.2. Several single nucleotide polymorphisms of the CTLA-4 gene have been identified. Some of these studies have demonstrated a significant association of CTLA-4 polymorphisms with atopy or asthma. However, the results were not consistent in other studies. Considering a single study may lack the power of providing a reliable conclusion, we performed a meta-analysis to investigate the relationship between CTLA-4 gene variants and asthma. To our knowledge, this is the first meta-analysis of the association between CTLA-4 polymorphisms and asthma susceptibility. A positive association between these polymorphisms and asthma could not be ruled out because studies with small sample size may have insufficient statistical power to detect a slight effect. Publication bias and heterogeneity may influence the results of meta-analyses. In our meta-analysis, only studies indexed by the selected databases were included. Negative studies were less likely to be published in journals and be available in computerized database, resulting in potential overestimation of effect sizes. In this meta-analysis, Begg’s test and Egger’s test showed significant publication bias, thus the current results should be interpreted cautiously. Therefore, heterogeneity did not seem to have influenced the results, suggesting the reliability of our results. Some limitations of this meta-analysis should be considered. First, the number of available studies that could be included was moderate. Therefore, the results could be influenced by factors like random error. Second, only 7 of the 17 studies were conducted in non-Asian population. Third, the overall outcomes were based on individual unadjusted ORs, while a more precise evaluation should be adjusted by other potentially suspected factors including age, sex and lifestyle.