title: Gene expression profiling to study racial differences after heart transplantation.
abstract: BACKGROUND
  The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.
  
  
  METHODS
  We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.
  
  
  RESULTS
  In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.
  
  
  CONCLUSIONS
  African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups.
authors.affiliation: Stanford University School of Medicine, Stanford, California. Electronic address: kiran@stanford.edu.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Khush
authors.affiliation: Stanford University School of Medicine, Stanford, California.
authors.forename: Michael X
authors.initials: MX
authors.lastname: Pham
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Teuteberg
authors.affiliation: Intermountain Medical Center, Salt Lake City, Utah.
authors.forename: Abdallah G
authors.initials: AG
authors.lastname: Kfoury
authors.affiliation: University of California at Los Angeles Medical Center, Los Angeles, California.
authors.forename: Mario C
authors.initials: MC
authors.lastname: Deng
authors.affiliation: Mid America Heart Institute, Saint Luke's Hospital, Kansas City, Missouri.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kao
authors.affiliation: University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Allen S
authors.initials: AS
authors.lastname: Anderson
authors.affiliation: Northwestern University School of Medicine, Chicago, Illinois.
authors.forename: William G
authors.initials: WG
authors.lastname: Cotts
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ewald
authors.affiliation: Newark Beth Israel Medical Center, Newark, New Jersey.
authors.forename: David A
authors.initials: DA
authors.lastname: Baran
authors.affiliation: CareDx Inc, Brisbane, California.
authors.forename: David
authors.initials: D
authors.lastname: Hiller
authors.affiliation: CareDx Inc, Brisbane, California.
authors.forename: James
authors.initials: J
authors.lastname: Yee
authors.affiliation: Stanford University School of Medicine, Stanford, California.
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Valantine
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006084:Graft Rejection / Q000208:ethnology / Q000235:genetics*; D006333:Heart Failure / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: acute rejection; calcineurin inhibitor; gene expression profile score; heart transplantation; mortality; race
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