Tissue-specific alternative splicing of TCF7L2
Prokunina-Olsson, Ludmila ; Welch, Cullan ; Hansson, Ola LU
; Adhikari, Neeta
; Scott, Laura J.
; Usher, Nicolle
; Tong, Maurine
; Sprau, Andrew
; Swift, Amy
and Bonnycastle, Lori L.
, et al.
(2009)
In Human Molecular Genetics
18(20).
p.3795-3804
- Abstract
- Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located... (More)
- Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r(2) = 0.84-0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164-FJ010174. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1489654
- author
- Prokunina-Olsson, Ludmila
; Welch, Cullan
; Hansson, Ola
LU
; Adhikari, Neeta
; Scott, Laura J.
; Usher, Nicolle
; Tong, Maurine
; Sprau, Andrew
; Swift, Amy
and Bonnycastle, Lori L.
, et al. (More)
- Prokunina-Olsson, Ludmila
; Welch, Cullan
; Hansson, Ola
LU
; Adhikari, Neeta
; Scott, Laura J.
; Usher, Nicolle
; Tong, Maurine
; Sprau, Andrew
; Swift, Amy
; Bonnycastle, Lori L.
; Erdos, Michael R.
; He, Zhi
; Saxena, Richa
; Harmon, Brennan
; Kotova, Olga
LU
; Hoffman, Eric P.
; Altshuler, David
; Groop, Leif
LU
; Boehnke, Michael
; Collins, Francis S.
and Hall, Jennifer L.
(Less)
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Human Molecular Genetics
- volume
- 18
- issue
- 20
- pages
- 3795 - 3804
- publisher
- Oxford University Press
- external identifiers
-
- wos:000270218300003
- scopus:70349569023
- ISSN
- 0964-6906
- DOI
- 10.1093/hmg/ddp321
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Metabolism (013212001), Diabetes and Endocrinology (013241530), Hypertension and Cardiovascular Disease (013242540)
- id
- 7ed61f51-dc13-4cc0-8468-29f5de441127 (old id 1489654)
- date added to LUP
- 2016-04-01 12:26:22
- date last changed
- 2024-02-07 09:54:01
@article{7ed61f51-dc13-4cc0-8468-29f5de441127,
abstract = {{Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of multiple TCF7L2 splicing forms in up to 380 samples from eight types of human tissue (pancreas, pancreatic islets, colon, liver, monocytes, skeletal muscle, subcutaneous adipose tissue and lymphoblastoid cell lines) and observed a tissue-specific pattern of alternative splicing. We tested whether the expression of TCF7L2 splicing forms was associated with single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D. Expression of two splicing forms was lower in pancreatic islets with increasing counts of T2D-associated alleles of the SNPs: a ubiquitous splicing form (P = 0.018 for rs7903146 and P = 0.020 for rs12255372) and a splicing form found in pancreatic islets, pancreas and colon but not in other tissues tested here (P = 0.009 for rs12255372 and P = 0.053 for rs7903146). Expression of this form in glucose-stimulated pancreatic islets correlated with expression of proinsulin (r(2) = 0.84-0.90, P < 0.00063). In summary, we identified a tissue-specific pattern of alternative splicing of TCF7L2. After adjustment for multiple tests, no association between expression of TCF7L2 in eight types of human tissue samples and T2D-associated genetic variants remained significant. Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164-FJ010174.}},
author = {{Prokunina-Olsson, Ludmila and Welch, Cullan and Hansson, Ola and Adhikari, Neeta and Scott, Laura J. and Usher, Nicolle and Tong, Maurine and Sprau, Andrew and Swift, Amy and Bonnycastle, Lori L. and Erdos, Michael R. and He, Zhi and Saxena, Richa and Harmon, Brennan and Kotova, Olga and Hoffman, Eric P. and Altshuler, David and Groop, Leif and Boehnke, Michael and Collins, Francis S. and Hall, Jennifer L.}},
issn = {{0964-6906}},
language = {{eng}},
number = {{20}},
pages = {{3795--3804}},
publisher = {{Oxford University Press}},
series = {{Human Molecular Genetics}},
title = {{Tissue-specific alternative splicing of TCF7L2}},
url = {{http://dx.doi.org/10.1093/hmg/ddp321}},
doi = {{10.1093/hmg/ddp321}},
volume = {{18}},
year = {{2009}},
}