title: Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients.
abstract: 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-alpha, interleukin (IL)-10, IL-6, interferon (IFN)-gamma, vascular endothelial growth factor (VEGF), transforming growth factor-beta1, Fas, FasL, granzyme B, ABCB1, CYP3A5.
  
  
  RESULTS
  Compared to Caucasians, African-Americans exhibited a higher prevalence of genotypes associated with low expression of IFN-gamma (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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Girnita
authors.forename: Steven A
authors.initials: SA
authors.lastname: Webber
authors.forename: Robert
authors.initials: R
authors.lastname: Ferrell
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Burckart
authors.forename: Maria M
authors.initials: MM
authors.lastname: Brooks
authors.forename: Kevin K
authors.initials: KK
authors.lastname: McDade
authors.forename: Richard
authors.initials: R
authors.lastname: Chinnock
authors.forename: Charles
authors.initials: C
authors.lastname: Canter
authors.forename: Linda
authors.initials: L
authors.lastname: Addonizio
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.forename: James K
authors.initials: JK
authors.lastname: Kirklin
authors.forename: Alin L
authors.initials: AL
authors.lastname: Girnita
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D016027:Heart Transplantation / Q000208:ethnology*; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins