Objective: To verify the association of transforming growth factor-beta(1)(TGF-beta(1)) (C-509T and T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) and ADAM33 (S_2) gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe persistent atopic asthma. Methods: A clinical, laboratory, prospective study was performed in patients with persistent atopic asthma, compared to a control group at Hospital Universitario da Universidade Estadual de Campinas between 2006 and 2007. Analysis of the TGF-beta(1) T869C gene polymorphism was performed using the technique polymerase chain reaction (PCR) + amplification refractory mutation system (ARMS). TGF-beta(1) C-509T, CD14 C-159T, IL-4 C-590T, IL-4Ra ILe50Val, and ADAM33 S2 gene polymorphisms were detected by PCR and restriction enzyme. Results: This study included 88 patients with persistent atopic asthma (27 mild, 23 moderate and 38 severe) and 202 healthy blood donors. As to T869C polymorphism (TGF-beta(1)), there was an association between the CC genotype and patients with severe asthma. There was no association in polymorphisms C-509T (TGF-beta(1)), C-590T (IL-4) and S_2 (ADAM33). When distribution of C-159T polymorphism genotype frequency (CD14) in severe asthma was compared with the control group, there was a significant result with the TT genotype. There was significant association of the Val/Val genotype (IL-4R) with mild asthma. Conclusion: Our results indicate that T869C (TGF-beta(1)), C-159T (CD14) and Val/Val (IL-4R) polymorphisms might be involved in modulation of asthma severity.843203210