IL-18 GENE POLYMORPHISM AND EXPRESSION CORRELATES WITH CORONARY VASCULOPATHY FOLLOWING TRANSPLANTATION.

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IL-18 GENE POLYMORPHISM AND EXPRESSION CORRELATES WITH CORONARY VASCULOPATHY FOLLOWING TRANSPLANTATION.
Olga D. McDaniel, Ph.D , Sani Yamout M.D. , Georgio Aru M.D. and Charles K. Moore, M.D. . Jackson MS, USA, University of MS Medical Center, 39216, Surgery ; Jackson MS, USA, University of MS Medical Center, 39216, Surgery and Jackson MS, USA, University of MS Medocal Center, 39216, Surgery .

Coronary vasculopathy (CV) is a major factor in the long-term survival of heart transplantation. The pathogenesis of CV in part is contributed to by the activation of immune responses of the recipient to the donor tissue. Evidence supports the role of cytokines in the inflammatory and immune responses that mediate allograft survival outcome. To test this hypothesis, peripheral blood mononuclear cells (PBMCs) from heart transplant patients were tested for their capacity to express different inflammatory cytokines at the mRNA level using a simple cytokine micrarrays. Blood samples were obtained from transplant patients with varying degrees of CV and/ or grade 3A rejections. Analysis of the hybridization pattern showed that IFN-α and γ , IL-18 and TNF-α L and TNF-β L were expressed in the PBMCs of patients with strong CV and patients with 3A/3B rejection. However, IL-18 was not present in patient’s PBMCs with mild or medium CV. The IL-18 expression was further confirmed by RT-PCR using mRNA from the same PBMCs. In addition, patients DNA samples were analyzed for IL-18 genotypes in association with CV. Comparing the distribution of IL-18 (high, intermediate, low) across levels of CV, we found 64.7% of patients with degrees of mild to strong CV carry IL-18 CC/GG high producer genotype, 29.4% IL-18 intermediate, and only 5.9% low genotype. Patients with no vasculopathy carry 35.6% IL-18 CC/GG high producer genotype but 53.3% intermediate and 11.1% low producing genotype (p<0.0006, RR=1.8). The molecular genetic data generated here could provide new information for improving the definition and classification of the onset of CV in allograft recipeints.