PMID- 25800097
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1753-0407 (Electronic)
IS  - 1753-0407 (Linking)
VI  - 8
IP  - 2
DP  - 2016 Mar
TI  - Differential promoter activity by nucleotide substitution at a type 2 diabetes 
      genome-wide association study signal upstream of the wolframin gene.
PG  - 253-9
LID - 10.1111/1753-0407.12289 [doi]
AB  - BACKGROUND: Functional knowledge of most genetic variants identified from 
      genome-wide association studies (GWAS) for type 2 diabetes (T2D) is limited. A 
      recent T2D GWAS revealed an association signal (rs4689388) upstream of the gene 
      encoding Wolfram syndrome 1 (WFS1) whose intrinsic nucleotide variants had been 
      previously associated with T2D in several candidate gene analyses. The aim of the 
      present study was to identify functional variants of the GWAS signal. METHODS: 
      Promoter activity of luciferase reporter constructs was compared with haplotypes 
      including variants composing a linkage disequilibrium block in the vicinity of 
      rs4689388 in HEK293 and HepG2 cells. RESULTS: Promoter activity was highest with 
      the most frequent haplotype (H1; ATCGT) and lowest with second most frequent 
      haplotype (H2; GATCG), whose nucleotide alleles were all complementary to those 
      of H1. Further analysis with artificial haplotypes revealed differential 
      transcriptional activity by nucleotide substitution of rs4320200, rs13107806, or 
      rs13127445 (P < 0.05). This concurred with changes in predicted transcription 
      factor binding site by their allele substitutions. CONCLUSIONS: The previously 
      reported GWAS signal for T2D may be identified by the differential promoter 
      activity of rs4320200, rs13107806, and rs13127445 in the promoter of WFS1 by 
      nucleotide substitution.
CI  - (c) 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley 
      Publishing Asia Pty Ltd.
FAU - Ryu, Jihye
AU  - Ryu J
AD  - School of Systems Biomedical Science, Soongsil University, Seoul, Korea.
FAU - Lee, Chaeyoung
AU  - Lee C
AD  - School of Systems Biomedical Science, Soongsil University, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150609
PL  - Australia
TA  - J Diabetes
JT  - Journal of diabetes
JID - 101504326
RN  - 0 (Membrane Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (wolframin protein)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Alleles
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Gene Expression Profiling
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study/*methods
MH  - HEK293 Cells
MH  - Haplotypes
MH  - Hep G2 Cells
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Luciferases/genetics/metabolism
MH  - Membrane Proteins/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic/*genetics
MH  - Transcription Factors/metabolism
OTO - NOTNLM
OT  - 2型糖尿病
OT  - genome-wide association
OT  - linkage disequilibrium
OT  - promoter activity
OT  - single nucleotide variant
OT  - type 2 diabetes
OT  - 全基因组关联
OT  - 单核苷酸变异
OT  - 启动子活性
OT  - 连锁不平衡
EDAT- 2015/03/25 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/03/25 06:00
PHST- 2014/09/11 00:00 [received]
PHST- 2015/02/09 00:00 [revised]
PHST- 2015/02/22 00:00 [accepted]
PHST- 2015/03/25 06:00 [entrez]
PHST- 2015/03/25 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1111/1753-0407.12289 [doi]
PST - ppublish
SO  - J Diabetes. 2016 Mar;8(2):253-9. doi: 10.1111/1753-0407.12289. Epub 2015 Jun 9.