INTERINDIVIDUAL CYTOKINE GENOTYPE VARIATION CORRELATES WITH ISCHEMIC CARDIOMYOPATHY AND MAY PREDICT THE OUTCOME OF CARDIAC TRANSPLANTATION

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TITLE: INTERINDIVIDUAL CYTOKINE GENOTYPE VARIATION CORRELATES WITH ISCHEMIC CARDIOMYOPATHY AND MAY PREDICT THE OUTCOME OF CARDIAC TRANSPLANTATION

Olga McDaniel,¹ Perrin Roten,¹ Vernetta Coleman,¹ Sani Yamout,¹ Maria Oropeza,¹ Charles Moore.²

¹Surgery, University of Mississippi Medical Center, Jackson, MS; ²Medicine, University of Mississippi Medical Center, Jackson, MS

Effectiveness of cytokine gene polymorphisms were evaluated in African–American (AA) and Caucasian (CAU) patients that had undergone cardiac transplantation (CTx). It has been suggested that allograft rejection is mediated by cytokines. Our working hypothesis is that the clinical condition of recipients before CTx might affect the outcome of allograft function through pre–existing genetic factors that are unique to each individual. Genomic DNA samples from 19 AA and 46 CAU recipients were tested by either single or multiplex PCR. Frequency distributions of genotypes were analyzed in respect to pre–CTx clinical characterization including coronary artery disease (CAD) and non–ischemic heart failure. The rejections were scored based on the number of biopsies graded greater than 2. Overall, the IL–10 high producer genotype was present in all patients graded as 1A and was significantly reduced in grade 2, 3A and 3B patients (28.6%, p = 0.02; 23%, p = 0.001; and 20%, p = 0.04, respectively). IFN–g A/A and IL–10 low producer genotypes were significantly increased in AA grade 3A recipients compared to CAU grade 3A recipients (47% vs 16.1%, p = 0.04; 76.5% vs 32.2%, p = 0.006 respectively). Both racial groups showed a high frequency of TGF–b1 high producer genotype compared with controls (AA: 70.5% vs 33.7%, p = 0.006; CAU: 71% vs 26.2%, p = 0.0001). There was a direct relationship between IFN–g T/T high producer and ischemic CAD as compared with IFN–A/A low producer and non–ischemic heart failure, supporting the influence of immunological factors in vasculopathy. In contrast, IL–2 T/T and IL–6 G/G high producer genotypes were present at a high frequency in AA recipients compared with CAU, with notable racial differences. These data indicate the importance that genotype analysis may have in understanding the pathophysiology of CTx outcome and may lead to better treatment options.