Genotypic variation and phenotypic characterization of granzyme B gene polymorphisms

Transplantation. 2009 Jun 27;87(12):1801-6. doi: 10.1097/TP.0b013e3181a755a4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Child
  • DNA Primers
  • Ethnicity
  • Genetic Variation*
  • Genotype
  • Graft Rejection / enzymology
  • Granzymes / genetics*
  • Heart Transplantation / immunology*
  • Heart Transplantation / pathology
  • Humans
  • Phenotype
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide*
  • Racial Groups
  • Reference Values

Substances

  • DNA Primers
  • Granzymes