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Association Between Promoter Polymorphisms in CD46 and CD59 in Kidney Donors and Transplant Outcome

Laura A Michielsen1, Arjan D van Zuilen1, Tineke Kardol-Hoefnagel2

  • 1Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Frontiers in Immunology
|June 6, 2018
PubMed

Insights

Donor gene variations in complement proteins CD46, CD55, and CD59 impact kidney transplant success. Specific CD59 and CD46 polymorphisms are linked to rejection and reduced graft survival, potentially guiding personalized treatment strategies.

Area of Science:

  • Immunogenetics
  • Transplant Immunology
  • Molecular Biology

Background:

  • Complement regulating proteins (CD46, CD55, CD59) protect cells from damage and are expressed on donor endothelium, suggesting a role in transplant accommodation.
  • Genetic variations (polymorphisms) in the promoter regions of these complement proteins may influence their expression levels.
  • Investigating donor polymorphisms in complement regulatory proteins could reveal novel factors influencing kidney transplant outcomes.

Purpose of the Study:

  • To determine if donor-derived polymorphisms in complement regulating proteins (CD46, CD55, CD59) affect kidney transplant outcomes.
  • To analyze the association between specific promoter polymorphisms and the risk of acute rejection and graft survival.

Main Methods:

  • Genotyping of five single nucleotide polymorphisms (SNPs) in the promoter regions of CD46, CD55, and CD59 in 306 kidney donors.
  • Statistical analysis including hazard ratios and p-values to assess the impact of polymorphisms on rejection-free survival and graft survival.

Main Results:

  • A CD59 promoter polymorphism (rs147788946) in donors was associated with significantly lower 1-year rejection-free survival and a trend towards impaired 5-year graft survival.
  • Two CD46 promoter polymorphisms (rs2796267 and rs2796268) were linked to reduced rejection-free survival in recipients.
  • The combined presence of favorable genotypes for CD46 (rs2796267) and CD59 (rs147788946) demonstrated a significant protective effect against acute rejection and improved graft survival.

Conclusions:

  • Donor polymorphisms in CD46 and CD59 promoter regions are significant predictors of kidney transplant outcomes, influencing rejection and graft survival.
  • These genetic markers can help identify recipients who may benefit from tailored immunosuppressive therapy or targeted complement inhibition strategies.
  • Further research into donor immunogenetics can optimize personalized medicine approaches in organ transplantation.

Keywords:
acute rejectioncomplement regulatory proteinsgeneticgraft survivalkidney donorpromoter regions

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