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

Richa Saxena; Lauren Gianniny; Noel P. Burtt; Valeriya Lyssenko; Candace Giuducci; Marketa Sjögren; Jose C. Florez; Peter Almgren; Bo Isomaa; Marju Orho-Melander; Ulf Lindblad; Mark J. Daly; Tiinamaija Tuomi; Joel N. Hirschhorn; Kristin G. Ardlie; Leif Groop; David Altshuler

doi:10.2337/db06-0381

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

Richa Saxena, Lauren Gianniny, Noel P. Burtt, Valeriya Lyssenko, Candace Giuducci, Marketa Sjögren, Jose C. Florez, Peter Almgren, Bo Isomaa, Marju Orho-Melander, Ulf Lindblad, Mark J. Daly, Tiinamaija Tuomi, Joel N. Hirschhorn, Kristin G. Ardlie, Leif Groop, David Altshuler

Translational Muscle Research

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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.

Original language	English
Pages (from-to)	2890-2895
Journal	Diabetes
Volume	55
Issue number	10
DOIs	https://doi.org/10.2337/db06-0381
Publication status	Published - 2006

Subject classification (UKÄ)

Endocrinology and Diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/db06-0381

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Saxena, R., Gianniny, L., Burtt, N. P., Lyssenko, V., Giuducci, C., Sjögren, M., Florez, J. C., Almgren, P., Isomaa, B., Orho-Melander, M., Lindblad, U., Daly, M. J., Tuomi, T., Hirschhorn, J. N., Ardlie, K. G., Groop, L., & Altshuler, D. (2006). Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes, 55(10), 2890-2895. https://doi.org/10.2337/db06-0381

@article{66968ad669724e40a88257d0ebf5cd0a,

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

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 = "Richa Saxena and Lauren Gianniny and Burtt, {Noel P.} and Valeriya Lyssenko and Candace Giuducci and Marketa Sj{\"o}gren and Florez, {Jose C.} and Peter Almgren and Bo Isomaa and Marju Orho-Melander and Ulf Lindblad and Daly, {Mark J.} and Tiinamaija Tuomi and Hirschhorn, {Joel N.} and Ardlie, {Kristin G.} and Leif Groop and David Altshuler",

year = "2006",

doi = "10.2337/db06-0381",

language = "English",

volume = "55",

pages = "2890--2895",

journal = "Diabetes",

issn = "1939-327X",

publisher = "American Diabetes Association Inc.",

number = "10",

}

Saxena, R, Gianniny, L, Burtt, NP, Lyssenko, V, Giuducci, C, Sjögren, M, Florez, JC, Almgren, P, Isomaa, B, Orho-Melander, M, Lindblad, U, Daly, MJ, Tuomi, T, Hirschhorn, JN, Ardlie, KG, Groop, L & Altshuler, D 2006, 'Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals', Diabetes, vol. 55, no. 10, pp. 2890-2895. https://doi.org/10.2337/db06-0381

TY - JOUR

T1 - Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals

AU - Saxena, Richa

AU - Gianniny, Lauren

AU - Burtt, Noel P.

AU - Lyssenko, Valeriya

AU - Giuducci, Candace

AU - Sjögren, Marketa

AU - Florez, Jose C.

AU - Almgren, Peter

AU - Isomaa, Bo

AU - Orho-Melander, Marju

AU - Lindblad, Ulf

AU - Daly, Mark J.

AU - Tuomi, Tiinamaija

AU - Hirschhorn, Joel N.

AU - Ardlie, Kristin G.

AU - Groop, Leif

AU - Altshuler, David

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.2337/db06-0381

DO - 10.2337/db06-0381

M3 - Article

C2 - 17003358

SN - 1939-327X

VL - 55

SP - 2890

EP - 2895

JO - Diabetes

JF - Diabetes

IS - 10

ER -

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

Abstract

Subject classification (UKÄ)

UN SDGs

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