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Updated: Jun 13, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Population-Specific Exploration of MIR146A Gene Polymorphism in Acute Renal Rejection: A Cross-Sectional,
Nor Elhouda Nacer1,2, Soumia Missoum3,4, Houssem Eddine Ouarhlent3,4
1Laboratory of Acquired and Constitutional Genetic Diseases (MAGECA), Faculty of Medicine, University of Batna 2, Batna 05000, Algeria.
Abstract:
Acute renal allograft rejection (AR) is immune-mediated. Recent evidence highlights some microRNAs as immune modulators. Few and conflicting studies have studied the impact of the MIR146A gene single-nucleotide polymorphism rs2910164 (C>G) on AR. We explored the association of rs2910164 with AR in a single-center cohort of 533 kidney transplant recipients (KTRs) by genotyping cases with biopsy-proven late AR (AR group, n = 35) and matched control KTRs without AR (non-AR group, n = 60). Genotyping was performed with real-time PCR. Multivariable logistic regression and Firth penalized logistic regression, as a sensitivity analysis, were used to adjust for confounding factors. Donor-recipient age difference was significantly higher in the AR group than in the non-AR group (23.37 ± 11.29 vs. 14.83 ± 10.54, p < 0.001). Recipient mean age in the AR group is lower than in the non-AR group (27.51 ± 10.34 vs. 32.83 ± 9.76 years, p = 0.014), while the opposite is observed with the donor mean age (49.57 ± 10.37 vs. 43.27 ± 10.27 years, p = 0.005). AR was associated with preformed donor-specific antibodies (DSAs) (45.7% vs. 8.3%, p = 0.000, OR = 9.263, 95% CI (2.988-28.720)), and with two HLA-A* mismatches (17.1% vs. 3.3%, p = 0.048, OR = 6.000, 95% CI (1.139-31.595)). Moreover, post-transplant viral infections, particularly with CMV and SARS-CoV-2, were associated with AR (p < 0.05). However, rs2910164 was not associated with AR across all the tested genetic models (p > 0.05). Our study provides population-specific negative association data on rs2910164 and AR. Larger multicentric studies and future meta-analyses are needed to clarify whether any effect is modest or context-dependent.
Insights
The rs2910164 polymorphism in the MIR146A gene is not associated with acute renal allograft rejection (AR) in kidney transplant recipients. This study provides population-specific data suggesting no link between this microRNA SNP and AR risk.
Area of Science:
- Immunogenetics
- Transplantation immunology
- Molecular biology
Background:
- Acute renal allograft rejection (AR) is a major complication following kidney transplantation, driven by immune responses.
- MicroRNAs are emerging as critical immune modulators, but their role in AR and specific genetic variants like the MIR146A rs2910164 polymorphism remain unclear.
- Previous studies on the association between MIR146A rs2910164 and AR have yielded few and conflicting results.
Purpose of the Study:
- To investigate the association between the MIR146A gene single-nucleotide polymorphism rs2910164 (C>G) and the risk of acute renal allograft rejection (AR).
- To analyze potential confounding factors, including donor-recipient age difference, donor-specific antibodies (DSAs), HLA mismatches, and post-transplant viral infections, in relation to AR.
- To provide population-specific data on the genetic contribution to AR susceptibility.
Main Methods:
- A cohort study involving 533 kidney transplant recipients (KTRs) was conducted.
- Genotyping for the MIR146A rs2910164 polymorphism was performed using real-time PCR in patients with biopsy-proven late AR (n=35) and matched controls without AR (n=60).
- Statistical analyses included multivariable logistic regression and Firth penalized logistic regression, adjusting for relevant clinical and immunological factors.
Main Results:
- The donor-recipient age difference was significantly higher in the AR group compared to the non-AR group (p < 0.001).
- AR was significantly associated with preformed donor-specific antibodies (DSAs) (OR = 9.263) and two HLA-A* mismatches (OR = 6.000).
- Post-transplant viral infections, including CMV and SARS-CoV-2, were also associated with AR (p < 0.05). Crucially, the rs2910164 polymorphism showed no significant association with AR across all tested genetic models (p > 0.05).
Conclusions:
- The MIR146A rs2910164 polymorphism is not associated with acute renal allograft rejection in the studied cohort of kidney transplant recipients.
- Factors such as donor-recipient age difference, DSAs, HLA mismatches, and viral infections are significant risk factors for AR.
- Larger, multicenter studies and meta-analyses are warranted to definitively confirm these findings and explore potential modest or context-dependent effects of rs2910164 on AR.
