Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients

BACKGROUND. Allograft failure in African-Americans remains higher than in Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with altered allograft outcomes. METHODS. In this multi-center study we compared SNP frequencies in 364 pediatric heart recipients from three ethnic/racial groups: Caucasian (n=243), African-American (n=39), and Hispanic (n=82). The target genes were: tumor necrosis factor-α, interleukin (IL)-10, IL-6, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), transforming growth factor-β1, Fas, FasL, granzyme B, ABCB1, CYP3A5. RESULTS. Compared to Caucasians, African-Americans exhibited a higher prevalence of genotypes associated with low expression of IFN-γ (24% vs. 45.7%, P<0.001) and IL-10 (33% vs. 57.1%, P=0.052). African-Americans also exhibited an increased prevalence of high IL-6 (82.9% vs. 38.1%; P<0.001). VEGF -2578 C/C and -460 C/C genotypes were found more frequently in African-Americans and Hispanics as compared to Caucasians (P<0.001). G/G genotype of Fas and T/T genotype of FasL were expressed more often by African-American recipients. The prevalence of Granzyme B (-295A/G) genotype was differentially distributed in the three groups. Compared with Caucasians, African-Americans were twice as likely to carry the ABCB1 2677 G/G genotype (78.6% vs. 33.7%, P<0.0025), and they were more frequent carriers of the CYP3A5 *1/*1 genotype (35.7% vs. 0.6% in Caucasians and 7.2% in Hispanics; P<0.001). CONCLUSION. African-Americans have a genetic background that may predispose to proinflammatory/lower regulatory environment, reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter study, these gene polymorphisms differences among ethnic/racial groups are being documented so that therapeutic strategies can be devised to optimize outcomes for pediatric transplant recipients.