Genotypic variation and phenotypic characterization of granzyme B gene polymorphisms

Diana M. Girnita, Steven A. Webber, Maria M. Brooks, Robert Ferrell, Alin L. Girnita, Gilbert J. Burckart, Richard Chinnock, Charles Canter, Linda Addonizio, Daniel Bernstein, James K. Kirklin, David Naftel, Adriana Zeevi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish
Pages (from-to)1801-1806
Number of pages6
Issue number12
StatePublished - Jun 27 2009


  • Gene polymorphism
  • Granzyme B
  • Heart
  • Pediatric
  • Transplantation


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