PMID- 23434931
OWN - NLM
STAT- MEDLINE
DCOM- 20130909
LR  - 20220309
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 62
IP  - 7
DP  - 2013 Jul
TI  - TCF7L2 variation and proliferative diabetic retinopathy.
PG  - 2613-7
LID - 10.2337/db12-1093 [doi]
AB  - Proliferative diabetic retinopathy (PDR) is the most severe vision-threatening 
      complication of diabetes. For investigation of genetic association between TCF7L2 
      and PDR in Caucasian type 2 diabetes mellitus (T2DM) and its functional 
      consequences, 383 T2DM patients with PDR (T2DM-PDR) and 756 T2DM patients without 
      diabetic retinopathy (T2DM-no DR) were genotyped with rs7903146 in TCF7L2. We 
      found that risk allele (T) frequency of rs7903146 was significantly higher in 
      T2DM-PDR patients (allelic P = 2.52E-04). In lymphoblastoid cells induced to 
      undergo endoplasmic reticulum (ER) stress by treatment of tunicamycin, higher 
      fold change of TCF7L2 and VEGFA mRNA levels were observed in rs7903146-TT cells 
      than in rs7903146-CC cells (P = 0.02 for TCF7L2; P = 0.004 for VEGFA), suggesting 
      that ER stress plays a role in PDR pathogenesis. Silencing TCF7L2 resulted in 
      decreased mRNA levels of both TCF7L2 and VEGFA (P < 0.001). Retinas of 
      oxygen-induced retinopathy mice (a model for PDR) had higher TCF7L2 and VEGFA 
      mRNA levels than those of controls (P = 2.9E-04 for TCF7L2; P = 1.9E-07 for 
      VEGFA). Together, data from our study show that TCF7L2-rs7903146 is associated 
      with PDR in Caucasian T2DM and suggest that TCF7L2 promotes pathological retinal 
      neovascularization via ER stress-dependent upregulation of VEGFA.
FAU - Luo, Jing
AU  - Luo J
AD  - Department of Ophthalmology, Second Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Zhao, Ling
AU  - Zhao L
FAU - Chen, Aaron Yun
AU  - Chen AY
FAU - Zhang, Xiaohui
AU  - Zhang X
FAU - Zhu, Jin
AU  - Zhu J
FAU - Zhao, Jiagang
AU  - Zhao J
FAU - Ouyang, Hong
AU  - Ouyang H
FAU - Luo, Hongrong
AU  - Luo H
FAU - Song, Yaojun
AU  - Song Y
FAU - Lee, Janet
AU  - Lee J
FAU - Patel, Sherrina H
AU  - Patel SH
FAU - Shaw, Peter X
AU  - Shaw PX
FAU - Sadda, Srinivas
AU  - Sadda S
FAU - Zhuo, Yehong
AU  - Zhuo Y
FAU - Rosenfeld, Michael G
AU  - Rosenfeld MG
FAU - Zhang, Kang
AU  - Zhang K
LA  - eng
GR  - P01 DK074868/DK/NIDDK NIH HHS/United States
GR  - TL1 RR031979/RR/NCRR NIH HHS/United States
GR  - R01 EY019270/EY/NEI NIH HHS/United States
GR  - R01 EY014428/EY/NEI NIH HHS/United States
GR  - 1TL1RR031979-01/RR/NCRR NIH HHS/United States
GR  - EY021374/EY/NEI NIH HHS/United States
GR  - T32 CA009523/CA/NCI NIH HHS/United States
GR  - EY018660/EY/NEI NIH HHS/United States
GR  - R01 EY018660/EY/NEI NIH HHS/United States
GR  - EY019270/EY/NEI NIH HHS/United States
GR  - EY014428/EY/NEI NIH HHS/United States
GR  - R01 EY021374/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130222
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Diabetic Retinopathy/*genetics
MH  - Endoplasmic Reticulum Stress/genetics
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Mice
MH  - *Polymorphism, Single Nucleotide
MH  - Retinal Neovascularization/genetics
MH  - Transcription Factor 7-Like 2 Protein/*genetics
MH  - Vascular Endothelial Growth Factor A/genetics
PMC - PMC3712060
EDAT- 2013/02/26 06:00
MHDA- 2013/09/10 06:00
PMCR- 2014/07/01
CRDT- 2013/02/26 06:00
PHST- 2013/02/26 06:00 [entrez]
PHST- 2013/02/26 06:00 [pubmed]
PHST- 2013/09/10 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - db12-1093 [pii]
AID - 1093 [pii]
AID - 10.2337/db12-1093 [doi]
PST - ppublish
SO  - Diabetes. 2013 Jul;62(7):2613-7. doi: 10.2337/db12-1093. Epub 2013 Feb 22.