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Abstract: PO2053

A Sliding Window Approach to Investigate the Role of Donor-Recipient Interindividual Genetic Distance on Kidney Transplant Outcome

Session Information

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Collins, Kane Edmund, Royal College of Surgeons in Ireland, Dublin, Ireland
  • Gilbert, Edmund H., Royal College of Surgeons in Ireland, Dublin, Ireland
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland
  • Lord, Graham M., The University of Manchester, Manchester, Manchester, United Kingdom
  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • Cavalleri, Gianpiero, Royal College of Surgeons in Ireland, Dublin, Ireland

Group or Team Name

  • Human Genetic Variation Research Group
Background

Although the role of HLA matching on kidney transplant outcome is well appreciated, the role of genetic matching between donors and recipients outside of the HLA region is less well understood. This is important as histological damage is a major issue in allografts and studies have suggested that non-HLA immune factors play a significant role in this process. However, the mechanism involved is presently unknown.
Previous studies on relatively small datasets have looked at the role of genetic distance on kidney transplant outcome and found significant effects on graft survival. The regions of the genome which may contain these genes have not yet been searched for. Several methods can estimate genetic distance (mismatch) such as IBS, which measures allelic sharing or IBD which measures haplotype sharing.

Methods

Using 2,122 genotyped donor-recipient pairs from the United Kingdom and Ireland Renal Transplant Consortium (UKIRTC), we performed a survival analysis using a Cox Proportional Hazards model, investigating the role of various clinical and genetic factors. We focused investigation on the impact of IBS and total length of IBD between donor and recipient on kidney transplant outcome. We then used a sliding window approach to test the association between mismatch at any autosomal region of the genome and graft survival. This used a sliding window of 3 million base pairs on both IBS and IBD, resulting in 947 regions of the genome to be tested for association.

Results


Several clinical covariates were found to be significantly associated with graft survival; graft number (Bonferroni-Holm p-value: 1.5 x 10-7), donor age (8 x 10-5) and total HLA mismatch (0.03). These are well established risk factors, confirming the veracity of our methodology. Although a window at the start of chromosome 6 in the HLA region was the most significant, we did not detect a statistically significant association between IBS or total length of IBD and graft survival after correction for multiple testing.

Conclusion

We were unable to find an association between either IBS or total length of IBD and graft survival. In addition, there was no particular region of the genome that had a significant association with survival (though the effect of the HLA region was the most significant).

Funding

  • Government Support – Non-U.S.