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Clin Transplant. 2018 Oct;32(10):e13395. doi: 10.1111/ctr.13395. Epub 2018 Oct 2.

Genomewide association study reveals novel genetic loci associated with change in renal function in heart transplant recipients.

Author information

1
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
2
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
3
Department of Biomedical Statistic and Informatics, Mayo Clinic, Rochester, Minnesota.
4
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.

Abstract

BACKGROUND:

Renal dysfunction occurs commonly after heart transplantation (HTx) with wide inter-individual variability but whether a genetic predisposition exists in these patients is unknown. Genomewide association studies (GWAS) have not been performed to assess the association of genetic variation with change in renal function after HTx.

METHODS:

Clinical and demographic data of patients who underwent HTx and provided blood samples and consent for genetic analysis were included. Genotyping was performed using Illumina Infinium Human CoreExome v1.0 analysis kit. A GWAS utilizing linear regression models was performed with estimated glomerular filtration rate (eGFR) at 1 year as the phenotype after adjusting for baseline eGFR prior to HTx and conversion from calcineurin inhibitor to sirolimus as primary immunosuppression therapy.

RESULTS:

A total of 251 HTx recipients were genotyped for 314,903 single nucleotide polymorphisms (SNPs). The mean (SD) age was 50 (12.5) years; most patients were of European origin (n = 243, 96.8%) and males (n = 179, 71.3%). After adjustment for potential confounders, two variants, rs17033285 (P = 4.3 × 10-7 ) and rs4917601 (P = 6.46 × 10-7 ), in a long non-coding RNA (lncRNA) gene LINC01121 and a pseudogene BTBD7P2, were identified to have a significant association with change in GFR at 1 year after HTx.

CONCLUSIONS:

Our first of its kind GWAS demonstrates that genetic variation affects renal function after HTx independent of other risk factors. Agnostic genetic approaches such as these may lead to identification of novel biological pathways such as the role of lncRNAs in the development of renal dysfunction post-HTx.

KEYWORDS:

genetic variation; genomewide association study; heart transplant; immunosuppression; nephrotoxicity; renal dysfunction

PMID:
30160337
DOI:
10.1111/ctr.13395

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