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.
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 PHTxpatients (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 BA-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: M V Clément; P Haddad; A Soulié; C Benvenuti; M G Lichtenheld; E R Podack; N Sigaux; M Sasportes Journal: Int Immunol Date: 1991-11 Impact factor: 4.823
Authors: Jeffrey L Veale; Leonard W Liang; Qiuheng Zhang; David W Gjertson; Zeying Du; Erik W Bloomquist; Juan Jia; Lei Qian; Alan H Wilkinson; Gabriel M Danovitch; Phuong-Thu T Pham; J Thomas Rosenthal; Charles R Lassman; Jonathan Braun; Elaine F Reed; H Albin Gritsch Journal: Hum Immunol Date: 2006-08-04 Impact factor: 2.850
Authors: B Corti; A Altimari; E Gabusi; A D Pinna; A Lauro; A M Morselli-Labate; E Gruppioni; M G Pirini; M Fiorentino; L Ridolfi; W F Grigioni; A D'Errico-Grigioni Journal: Transplant Proc Date: 2005-12 Impact factor: 1.066
Authors: L M Vasconcellos; A D Schachter; X X Zheng; L H Vasconcellos; M Shapiro; W E Harmon; T B Strom; D Schachter Journal: Transplantation Date: 1998-09-15 Impact factor: 4.939
Authors: A D'Errico; B Corti; A D Pinna; A Altimari; E Gruppioni; E Gabusi; M Fiorentino; A Bagni; W F Grigioni Journal: Transplant Proc Date: 2003-12 Impact factor: 1.066