Genotypic variation and phenotypic characterization of granzyme B gene polymorphisms

Academic Article

Abstract

  • BACKGROUND.: Granzyme B has been associated with allograft rejection in solid organ transplantation. Single nucleotide polymorphisms (SNPs) in the granzyme B gene might impact its expression. The aims of this study were (1) to establish the frequency of two granzyme B SNPs (A-295G; Q-55R) in pediatric heart transplant (PHTx) recipients and (2) to determine their phenotypic expression in healthy individuals. METHODS.: Three hundred ninety-six PHTx patients (245 white non-Hispanic, 49 black non-Hispanic, 82 Hispanics, and 20 others) and 52 healthy controls were screened for Q-55R and A-295G. For the control samples, we assessed the frequency of granzyme B positive cells by ELISPOT assay after mitogen stimulation. RESULTS.: Among the PHTx recipients, 57% percent of the population carried the Q/Q genotype, whereas 6% were R/R homozygotes. Seven of 49 (14%) black non-Hispanics were R/R homozygotes, whereas 13 of 245 (5%) of white non-Hispanics and 5 of 82 (6%) Hispanics carried the R/R genotype (P=0.02). The A allele frequency of granzyme B A-295G (49.6%) was similar to that of the G allele (50.4%). However, 80% of Black non-Hispanics were A allele carriers compared with 68% of White non-Hispanics (P<0.0001). After mitogen stimulation, the frequency of granzyme B positive cells was higher in the Q/Q homozygotes compared with R/R carriers (P=0.006), whereas a similar frequency of granzyme B positive cells was noticed among the genotypes of A-295G SNP. CONCLUSIONS.: These data indicate that 55 Q/Q genotype is associated with increased in vitro expression of granzyme B. © 2009 by Lippincott Williams & Wilkins.
  • Authors

    Published In

  • Transplantation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Girnita DM; Webber SA; Brooks MM; Ferrell R; Girnita AL; Burckart GJ; Chinnock R; Canter C; Addonizio L; Bernstein D
  • Start Page

  • 1801
  • End Page

  • 1806
  • Volume

  • 87
  • Issue

  • 12