AIMS: Interleukin- (IL-) 6 is a pleiotropic cytokine with effects on the acute phase response, inflammation, and vascular function. A G to C polymorphism has been described at position -174 in the promoter region of the IL-6 gene. We investigated the influence of this polymorphism on the development of cardiac transplant related coronary vasculopathy (CV). METHODS: Sequence specific polymerase chain reaction identified the -174*G/C allele for 116 cardiac transplant recipients. Coronary disease was identified by routine surveillance post-transplant coronary angiography. RESULTS: Prevalence of the -174*G/C polymorphism was different between the transplant and control cohorts; *CC 27.6%, *CG 45.7%, and *GG 26.7% vs. 13.2%, 44.1% and 42.7% respectively (p = 0.004). Median time to the first diagnosis of CV was different between the 3 alleles; *CC 2.8 years (2.0-4.0); *CG 3.9 years (2.1-4.5); *GG 5.3 years (3.2-6.1) (p = 0.05). By Kaplan-Meier survival analysis C homozygotes developed CV significantly earlier than the other cohorts (p = 0.035). At 5 years 100% of C homozygotes had evidence for CV. G homozygotes had a more gradual onset of CV with an approximate 60% prevalence at 5 years. *CC genotype was the most predictive risk factor for CV development (Hazard ratio 4.2 (95% CI 1.3-12.9); p = 0.014). Increasing donor age was also significant (Hazard ratio 1.04 (95% CI, 1.0-1.08); p = 0.023). CONCLUSIONS: Polymorphism at position -174 within the promoter region of the IL-6 gene may be an important risk factor for cardiac transplant related coronary vasculopathy. This may improve patient selection and allow tailored immunosuppressive treatment.
AIMS: Interleukin- (IL-) 6 is a pleiotropic cytokine with effects on the acute phase response, inflammation, and vascular function. A G to C polymorphism has been described at position -174 in the promoter region of the IL-6 gene. We investigated the influence of this polymorphism on the development of cardiac transplant related coronary vasculopathy (CV). METHODS: Sequence specific polymerase chain reaction identified the -174*G/C allele for 116 cardiac transplant recipients. Coronary disease was identified by routine surveillance post-transplant coronary angiography. RESULTS: Prevalence of the -174*G/C polymorphism was different between the transplant and control cohorts; *CC 27.6%, *CG 45.7%, and *GG 26.7% vs. 13.2%, 44.1% and 42.7% respectively (p = 0.004). Median time to the first diagnosis of CV was different between the 3 alleles; *CC 2.8 years (2.0-4.0); *CG 3.9 years (2.1-4.5); *GG 5.3 years (3.2-6.1) (p = 0.05). By Kaplan-Meier survival analysis C homozygotes developed CV significantly earlier than the other cohorts (p = 0.035). At 5 years 100% of C homozygotes had evidence for CV. G homozygotes had a more gradual onset of CV with an approximate 60% prevalence at 5 years. *CC genotype was the most predictive risk factor for CV development (Hazard ratio 4.2 (95% CI 1.3-12.9); p = 0.014). Increasing donor age was also significant (Hazard ratio 1.04 (95% CI, 1.0-1.08); p = 0.023). CONCLUSIONS: Polymorphism at position -174 within the promoter region of the IL-6 gene may be an important risk factor for cardiac transplant related coronary vasculopathy. This may improve patient selection and allow tailored immunosuppressive treatment.
Authors: Khurram Shahzad; Martin Cadeiras; Sarfaraz Memon; Barry Zeeberg; Tod Klingler; Anshu Sinha; Esteban G Tabak; Sreevalsa Unniachan; Mario C Deng Journal: J Transplant Date: 2010-12-28
Authors: Herwig P Moll; Andy Lee; Clayton R Peterson; Jesus Revuelta Cervantes; Brandon M Wojcik; Anshul Parulkar; Alessandra Mele; Philip J LoGerfo; Jeffrey J Siracuse; Eva Csizmadia; Cleide G da Silva; Christiane Ferran Journal: Transplantation Date: 2016-11 Impact factor: 4.939