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Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals

Saxena, Richa ; Gianniny, Lauren ; Burtt, Noel P. ; Lyssenko, Valeriya LU ; Giuducci, Candace ; Sjögren, Marketa LU ; Florez, Jose C. ; Almgren, Peter LU ; Isomaa, Bo and Orho-Melander, Marju LU , et al. (2006) In Diabetes 55(10). p.2890-2895
Abstract
Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers,... (More)
Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers, P = 0.003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
55
issue
10
pages
2890 - 2895
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:17003358
  • wos:000240910400029
  • scopus:33750892139
  • pmid:17003358
ISSN
1939-327X
DOI
10.2337/db06-0381
language
English
LU publication?
yes
id
66968ad6-6972-4e40-a882-57d0ebf5cd0a (old id 389625)
date added to LUP
2016-04-01 16:35:09
date last changed
2021-10-03 05:27:42
@article{66968ad6-6972-4e40-a882-57d0ebf5cd0a,
  abstract     = {Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers, P = 0.003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes.},
  author       = {Saxena, Richa and Gianniny, Lauren and Burtt, Noel P. and Lyssenko, Valeriya and Giuducci, Candace and Sjögren, Marketa and Florez, Jose C. and Almgren, Peter and Isomaa, Bo and Orho-Melander, Marju and Lindblad, Ulf and Daly, Mark J. and Tuomi, Tiinamaija and Hirschhorn, Joel N. and Ardlie, Kristin G. and Groop, Leif and Altshuler, David},
  issn         = {1939-327X},
  language     = {eng},
  number       = {10},
  pages        = {2890--2895},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals},
  url          = {http://dx.doi.org/10.2337/db06-0381},
  doi          = {10.2337/db06-0381},
  volume       = {55},
  year         = {2006},
}