title: Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus.
abstract: BACKGROUND
  Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after renal transplantation. Activation of the innate immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of insulin resistance and deficiency. Although links between diabetes, dysregulated innate immune responses, and the TLR signaling pathway have been reported, no study so far has investigated their associations with PTDM. In this study, we ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated with PTDM in the Korea population.
  
  
  METHODS
  A total of 305 patients who received renal transplants without previously diagnosed diabetes were included. We analyzed the association between PTDM development and 6 SNPs within 2 genes of TLR2, 1 gene of TLR4, and 3 genes of TRL6.
  
  
  RESULTS
  Of 305 patients, PTDM developed in 51 patients (16.6%). Patients in the PTDM group were older than those in the non-PTDM group (45.56 ± 1.28 vs. 38.28 ± 0.71 years). Patients with PTDM had significantly higher allele frequency compared to those without PTDM for the TLR4 rs1927914*T, TLR6 rs3775073*A, TLR6 rs3821985*C, and TLR6 rs1039559*C alleles. Of the 6 SNPs, rs1927914 in the TLR4 gene and rs1039559 in the TLR6 gene were significantly associated with the development of PTDM after adjustment for age, gender, and tacrolimus usage.
  
  
  CONCLUSIONS
  Our study demonstrates a significant association between SNPs rs1927914 in TLR4 and rs1039559 in TLR6 and PTDM in the renal transplantation recipient group. These data suggest that the activation of the innate immune system and inflammation via TLR activation might have an essential role in the pathogenesis of PTDM in renal transplantation.
authors.affiliation: Division of Nephrology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jin Sug
authors.initials: JS
authors.lastname: Kim
authors.forename: Seul Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Park
authors.forename: Yang Gyun
authors.initials: YG
authors.lastname: Kim
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Moon
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Chun Gyoo
authors.initials: CG
authors.lastname: Ihm
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Lee
authors.forename: Su Kang
authors.initials: SK
authors.lastname: Kim
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Chung
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Kang
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Kim
authors.forename: Yeong Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Jeong
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000209:etiology*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; C495368:TLR6 protein, human; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors