Two Promoter Polymorphisms in the Genes Encoding for Complement Regulating Proteins CD46 and CD59 in Kidney Donors Are Associated with Biopsy Proven Acute Rejection.

L. Michielsen,¹ A. van Zuilen,¹ T. Kardol-Hoefnagel,² M. Verhaar,¹ H. Otten.²

¹Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands
²Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands

Meeting: 2017 American Transplant Congress

Abstract number: B39

Keywords: Gene polymorphism, Graft survival, Kidney transplantation

Session Information

Session Name: Poster Session B: Allorecognition and T Cell Biology

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background

Complement regulating proteins, including CD46, CD55 and CD59, protect cells against self-damage. Because of their expression on the donor endothelium, they are hypothesized to be involved in accommodation. Polymorphisms in their promoter regions may affect transcription. The aim of this study was to investigate if donor polymorphisms in complement regulating proteins influence kidney transplant outcomes.

Methods

We have included 317 kidney transplantations between 2005 and 2010. Five polymorphisms in the promoters of CD46 (rs2796267 and rs2796268), CD55 (rs150046210 and rs283715831) and CD59 (rs147788946) were genotyped. Log-rank analyses were used to compare survival curves.

Results

The absence of an insertion in the CD59 promoter (rs147788946) of donors was associated with a lower freedom from biopsy proven acute rejection or acute borderline rejection (BPAR) within the first year (p=0.04). Although the 5-year graft survival curve suggests an impaired graft survival this was not significant (p=0.13). Furthermore, for a single nucleotide polymorphism (SNP) in the CD46 promoter (rs2796267, A/G) we found that the presence of at least one G allele resulted in a lower freedom from BPAR within the first year (p=0.03). There was no correlation with 5-year graft survival (p=0.73). Next, we compared the presence of both protective genotypes in donors (n=24) to the presence of both risk genotypes (n=145). The results indicated an even more distinct difference in freedom from BPAR within the first year (p=0.007). Moreover, the presence of both protective genotypes was also correlated with an improved 5-year graft survival (p=0.04). Finally, a second SNP in the CD46 promoter (rs2796268, A/G) showed a trend towards a lower freedom from BPAR in the presence of at least one G allele (p=0.08). CD55 promoter SNPs did not significantly correlate with transplant outcomes.

Conclusions

These results suggest that two promoter polymorphisms in CD46 (rs2796267) and CD59 (rs147788946) in kidney donors correlate with a lower freedom from BPAR within the first year. Although numbers are relatively low, the combined presence of both protective genotypes appeared to have an additional preservative effect on freedom from BPAR and 5-year graft survival.

CITATION INFORMATION: Michielsen L, van Zuilen A, Kardol-Hoefnagel T, Verhaar M, Otten H. Two Promoter Polymorphisms in the Genes Encoding for Complement Regulating Proteins CD46 and CD59 in Kidney Donors Are Associated with Biopsy Proven Acute Rejection. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Michielsen L, Zuilen Avan, Kardol-Hoefnagel T, Verhaar M, Otten H. Two Promoter Polymorphisms in the Genes Encoding for Complement Regulating Proteins CD46 and CD59 in Kidney Donors Are Associated with Biopsy Proven Acute Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/two-promoter-polymorphisms-in-the-genes-encoding-for-complement-regulating-proteins-cd46-and-cd59-in-kidney-donors-are-associated-with-biopsy-proven-acute-rejection/. Accessed May 12, 2025.

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