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LIMS1 risk genotype and T cell–mediated rejection in kidney transplant recipients

Authors :
Mehmet Sukru Sever
Ahmet Burak Dirim
Aydin Turkmen
Sebahat Akgul
Safak Mirioglu
John C. Edwards
Fatma Oguz Savran
Yasar Caliskan
Ali G. Gharavi
Gonca E. Karahan
Halil Yazici
Krista L. Lentine
Krzysztof Kiryluk
Yasemin Ozluk
Erol Demir
MİRİOĞLU, ŞAFAK
Source :
Nephrology Dialysis Transplantation. 36:2120-2129
Publication Year :
2021
Publisher :
Oxford University Press (OUP), 2021.

Abstract

Background This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort. Methods We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell–mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss. Results After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG genotype (n = 200) compared with the AA/AG genotypes (n = 641) [25 (12.5%) versus 35 (5.5%); P = 0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44–4.12); P = 0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan–Meier estimates of 5-year (94.3% versus 94.4%; P = 0.99) and 10-year graft survival rates (86.9% versus 83.4%; P = 0.31) did not differ significantly in the GG versus AA/AG groups. Conclusions Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype.

Details

ISSN :
14602385 and 09310509
Volume :
36
Database :
OpenAIRE
Journal :
Nephrology Dialysis Transplantation
Accession number :
edsair.doi.dedup.....2456bf472e931891f74b0fadb413339c
Full Text :
https://doi.org/10.1093/ndt/gfab168