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 LIMS1 rs893403 variant by Sanger sequencing followed by PCR confirmation of the deletion. Recipients who were homozygous for LIMS1 rs893403 genotype GG were compared to AA/AG genotypes. The primary outcome was T-cell mediated (TCMR) or antibody mediated rejection (ABMR) 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 (n = 200) compared to AA/AG (n = 641) genotypes [25 (12.5%) vs 35 (5.5%); p = 0.001] while ABMR did not differ by genotype [18 (9.0%) vs 62 (9.7%)]. Recipients with GG genotype had 2.4-times higher risk of TCMR than those who did not have this genotype (adjusted hazard ratio (aHR), 1.442.434.12, p = 0.001). A total of 189 (22.5%) recipients lost their allografts during follow up. Kaplan-Meier estimates of 5-year (94.3% vs. 94.4%, p = 0.99) and 10-year graft survival rates (86.9% vs. 83.4%, p = 0.31) did not differ significantly in those with GG compared to AA/AG groups.
Conclusions: Our study demonstrates that recipient LIMS1 risk genotype is associated with increased risk of TCMR after kidney transplantation, confirming the role of 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.