Association Between TLR2, TLR4, and CD14 Gene Polymorphisms and Acute Rejection in Kidney Transplant

Abstract

Objectives: Toll-like receptors play an important role in innate and adaptive immune responses and can induce acute graft rejection, especially in the early phase after transplant. The aim of this study was to evaluate the possible association between TLR2, TLR4, and CD14 polymorphisms and acute renal rejection.

Materials and methods: Our study included 239 patients seen between 2013 and 2015. Patients were classified into 3 groups: acute rejection group (71 patients), stable graft function group (71 patients), and healthy control group (97 patients). Polymorphisms in TLR2 (Arg753Gln, rs5743708), TLR4 (Asp299Gly, rs4986790; Thr399Ile, rs4986791), and CD14 (-159C/T, rs2569190) were determined by the TaqMan allelic discrimination assay for detection of single-nucleotide polymorphisms.

Results: The genotype distribution of CD14 rs2569190C/T was found to be significantly different among the acute rejection, stable graft function, and healthy control groups (P < .05). Interestingly, based on logistic regression, CD14 genotype (rs2569190) in patients with acute rejection was still significant after including risk factors. The adjusted odds ratio for CD14 CT+TT over CC genotype was calculated as 3.172 (95% confidence interval, 1.397-7.200; P = .006). Moreover, incidence of acute rejection and graft loss were significantly more frequent in recipients carrying CD14 TT (95% confidence interval, 2.81-27.16; P ≤ .001). In contrast to CD14, no significant differences were observed in the single-nucleotide polymorphisms of TLR2 and TLR4 genes in the acute rejection group versus the stable graft function and healthy control groups. The presence of CD14 T allele was associated with a significantly lower rejection-free survival compared with the CD14 CT and CC genotypes (P ≤ .001).

Conclusions: Renal transplant recipients carrying the CD14-159 TT genotype have significantly higher risk of acute rejection and reduced transplant survival rate than patients with heterozygous or wild-type genotypes.