Association studies of Toll-like receptor gene polymorphisms with allograft survival in renal transplant recipients of North India

作者:Srivastava Priyanka; Singh Anugya; Kesarwani Praveen; Jaiswal Praveen K; Singh Vibha; Mittal Rama D*
来源:Clinical Transplantation, 2012, 26(4): 581-588.
DOI:10.1111/j.1399-0012.2011.01577.x

摘要

Srivastava P, Singh A, Kesarwani P, Jaiswal PK, Singh V, Mittal RD. Association studies of Toll-like receptor gene polymorphisms with allograft survival in renal transplant recipients of North India. Abstract: Organ transplantation itself inevitably activates the innate immune system by Toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association of TLR2, TLR3, and TLR9 polymorphisms of donor-recipient pairs and acute rejection in renal transplant patients of North India. TLR2 (-196 to -174 del), TLR3 (c.1377C/T; rs 3775290), and TLR9 (+2848 G/A; rs 352140) were genotyped using DNA samples from 200 donor-recipient pairs of live donor kidney transplantation by applying Restriction Fragment Length Polymorphism (RFLP) methodology. The variant allele frequency of TLR2 (-196 to -174 del) was significantly different between recipients and donors (7.5% vs. 5.0%; p = 0.049; OR = 3.9; 95%CI = 1.0115.32). However, no significant association for allograft rejection was observed in transplant recipients for TLR3 and TLR9. Interestingly, a low prevalence of AA genotype of TLR9 + 2848 G>A was observed in rejecters when compared with non-rejecters, demonstrating protective association with allograft rejection (OR = 0.30, 95% CI = 0.120.88, p = 0.028). An allele in patients was also observed to be associated with higher rejection-free survival (log-rank = 0.044). These TLR gene polymorphisms, upon further evaluation, may be helpful in elucidation of immunobiological mechanisms associated with renal graft rejection.