title: 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 = 1.01-15.32). 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 = 0.12-0.88, 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.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Srivastava
authors.forename: Anugya
authors.initials: A
authors.lastname: Singh
authors.forename: Praveen
authors.initials: P
authors.lastname: Kesarwani
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Jaiswal
authors.forename: Vibha
authors.initials: V
authors.lastname: Singh
authors.forename: Rama D
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000235:genetics* / Q000401:mortality; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D015996:Survival Rate; D014019:Tissue Donors; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9