The TGF-B1 and IL-10 gene polymorphisms are associated with risk of developing silent myocardial ischemia in the diabetic patients.
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-β1-509 T>C (rs1800469), and TGF-β1 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, Pdom=0.029 and OR=1.69, PHet=0.043). On the other hand, the TGF-β1 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, Pdom=0.035, OR=1.50, Padd=0.026). Finally, the TGF-β1 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, PCod=0.004, OR=2.24, Pdom=0.002, OR=2.46, Prec=0.03 and OR=1.94, Padd=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-β1-509 T>C (rs1800469), and TGF-β1 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-β1 for SMI development.
Medical Biochemistry Unit of the Specialities Hospital, Centro Médico Nacional Siglo XXI-Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Miguel
M
Cruz
José Manuel
JM
Fragoso
Edith
E
Alvarez-León
Jorge
J
Escobedo-de-la-Peña
Adan
A
Valladares
Teresa
T
Juárez-Cedillo
Oscar
O
Pérez-Méndez
Gilberto
G
Vargas-Alarcón
D000368:Aged; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1; D016753:Interleukin-10
Genetic susceptibility; Haplotypes; Interleukin 10; Polymorphisms; Silent myocardial ischemia; Transforming growth factor-β1