title: Genotypic variation and phenotypic characterization of granzyme B gene polymorphisms.
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.
authors: Department of Pathology, Thomas E Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors: Diana M
authors: DM
authors: Girnita
authors: Steven A
authors: SA
authors: Webber
authors: Maria M
authors: MM
authors: Brooks
authors: Robert
authors: R
authors: Ferrell
authors: Alin L
authors: AL
authors: Girnita
authors: Gilbert J
authors: GJ
authors: Burckart
authors: Richard
authors: R
authors: Chinnock
authors: Charles
authors: C
authors: Canter
authors: Linda
authors: L
authors: Addonizio
authors: Daniel
authors: D
authors: Bernstein
authors: James K
authors: JK
authors: Kirklin
authors: David
authors: D
authors: Naftel
authors: Adriana
authors: A
authors: Zeevi
mesh_terms: D002648:Child; D017931:DNA Primers; D005006:Ethnicity; D014644:Genetic Variation; D005838:Genotype; D006084:Graft Rejection / Q000201:enzymology; D053804:Granzymes / Q000235:genetics*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D012016:Reference Values
chemical_list: D017931:DNA Primers; D053804:Granzymes