Silent myocardial ischemia (SMI) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. Considering the prominent role of IL-10 and TGF-B1 as regulators of the inflammatory process and vascular physiology, the aim of the present study was to analyze whether IL-10 and TGF-B1 single nucleotide polymorphisms (SNPs) are associated with SMI. The IL-10-1082 A>G (rs1800896), IL-10-819 T>C (rs1800871), IL-10-592 A>C (rs1800872), TGF-beta 1-509 T>C (rs1800469), and TGF-beta 1 T29C (rs1800470) SNPs were analyzed by 5'exonuclease TaqMan genotyping assays in a group of 149 SMI patients and 248 healthy controls. The IL-10-1082 A>G (rs1800896) SNP was significantly associated with an increased risk of SMI as compared to controls under both dominant and heterozygous models (OR = 1.77, P-dom = 0.029 and OR = 1.69, P-Het = 0.043). On the other hand, the TGF-beta 1 509 T>C (rs1800469) SNP was significantly associated with increased risk of SMI as compared to controls under a dominant and additive models (OR = 1.82, P-dom = 0.035, OR = 1.50, P-add = 0.026). Finally, the TGF-beta 1 T29C(rs1800470) SNP was significantly associated with increased risk of SMI as compared to controls under a co-dominant, dominant, recessive, and additive models (OR = 3.63, P-Cod = 0.004, OR = 2.24, P-dom = 0.002, OR = 2.46, P-rec = 0.03 and OR = 1.94, P-add = 0.001). After adjusted for gender, age, and smoking, two haplotypes (CC and TT) were associated with decreased risk of SMI (OR = 0.26, P<0.0001 and OR = 0.15, P = 0.017). In summary, our data suggest that the IL-10-1082 A>G (rs1800896), TGF-beta 1-509 T>C (rs1800469), and TGF-beta 1,91 T29C (rs1800470) SNPs play an important role in the risk of developing SMI. In our study, it was possible to distinguish two protective haplotypes in TGF-beta 1 for SMI development. (C) 2013 Elsevier B.V. All rights reserved.