PMID- 21857094
OWN - NLM
STAT- MEDLINE
DCOM- 20111214
LR  - 20200106
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Linking)
VI  - 63
IP  - 3
DP  - 2011
TI  - Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with 
      posttransplant diabetes mellitus in kidney transplant patients medicated with 
      tacrolimus.
PG  - 826-33
AB  - New onset posttransplant diabetes mellitus (PTDM) has a high incidence after 
      kidney transplantation in patients medicated with tacrolimus. PTDM can adversely 
      affect patient and graft survival. The pathophysiology of PTDM closely mimics 
      type 2 diabetes mellitus (T2DM). One of the possible genetic factors predisposing 
      individuals to PTDM might be a polymorphism in the transcription factor 7-like 2 
      gene (TCF7L2). This polymorphism has previously been associated with increased 
      risk of T2DM in the general population. Therefore, the present study aimed to 
      evaluate TCF7L2 polymorphisms in PTDM in kidney transplant patients medicated 
      with tacrolimus. Non-diabetic kidney transplant patients medicated with 
      tacrolimus (n = 234) were genotyped for the presence of TCF7L2 gene variants 
      (rs12255372 and rs7903146) using TaqMan probes. Of the 234 patients, 66 patients 
      had developed PTDM and 168 had not. Frequencies of the studied single nucleotide 
      polymorphisms (SNPs) did not differ significantly between the study groups. 
      Moreover, haplotype analyses failed to detect any associations between TCF7L2 
      haplotypes and PTDM. However, in late-onset PTDM (developed later that 2 weeks 
      from transplantation), frequencies of the rs7903146 TT genotype and T minor 
      allele were significantly increased compared to non-PTDM controls (17.9% vs. 
      5.9%, p = 0.017, OR: 4.13, 95% CI: 1.19-14.33 for TT genotype, 39.3% vs. 25.9%, p 
      = 0.038 for T allele). If the application of TCF7L2 rs7903146 SNPs as a marker 
      for PTDM is confirmed by further independent studies, replacing tacrolimus with 
      other immunosuppressants could be warranted in patients at high risk of PTDM, as 
      diagnosed by TCF7L2 genotyping.
FAU - Kurzawski, Mateusz
AU  - Kurzawski M
AD  - Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72, 
      PL 70-111 Szczecin, Poland.
FAU - Dziewanowski, Krzysztof
AU  - Dziewanowski K
FAU - Kedzierska, Karolina
AU  - Kedzierska K
FAU - Wajda, Anna
AU  - Wajda A
FAU - Lapczuk, Joanna
AU  - Lapczuk J
FAU - Drozdzik, Marek
AU  - Drozdzik M
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adult
MH  - Diabetes Mellitus, Type 2/*chemically induced/genetics
MH  - Female
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/therapeutic use
MH  - Kidney Transplantation/*methods
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction/methods
MH  - Polymorphism, Single Nucleotide
MH  - Tacrolimus/*adverse effects/therapeutic use
MH  - Transcription Factor 7-Like 2 Protein/*genetics
EDAT- 2011/08/23 06:00
MHDA- 2011/12/15 06:00
CRDT- 2011/08/23 06:00
PHST- 2010/09/29 00:00 [received]
PHST- 2010/11/29 00:00 [revised]
PHST- 2011/08/23 06:00 [entrez]
PHST- 2011/08/23 06:00 [pubmed]
PHST- 2011/12/15 06:00 [medline]
AID - S1734-1140(11)70595-3 [pii]
AID - 10.1016/s1734-1140(11)70595-3 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2011;63(3):826-33. doi: 10.1016/s1734-1140(11)70595-3.