Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.

<h4>Background</h4>Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary at...

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Autores principales:	Axel Muendlein, Christoph H Saely, Simone Geller-Rhomberg, Gudrun Sonderegger, Philipp Rein, Thomas Winder, Stefan Beer, Alexander Vonbank, Heinz Drexel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ea521dcd5ff644ad90f0ac0f3f485a2a
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spelling	oai:doaj.org-article:ea521dcd5ff644ad90f0ac0f3f485a2a2021-11-18T06:57:18ZSingle nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.1932-620310.1371/journal.pone.0017978https://doaj.org/article/ea521dcd5ff644ad90f0ac0f3f485a2a2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423583/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients.<h4>Methodology/principal findings</h4>We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR = 1.29 [1.09-1.53]; p = 0.003). This association was strong and significant in T2DM patients (n = 393; OR = 1.91 [1.32-2.75]; p = 0.001) but not in non-diabetic subjects (OR = 1.09 [0.90-1.33]; p = 0.370). The interaction risk allele by T2DM was significant (p(interaction) = 0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR = 1.90 [1.31-2.74]; p = 0.001 and OR = 1.75 [1.22-2.50]; p = 0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR = 1.22 [1.04-1.43]; p = 0.013 and OR = 1.67 [1.19-2.22]; p = 0.003, respectively).<h4>Conclusions/significance</h4>These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis.Axel MuendleinChristoph H SaelySimone Geller-RhombergGudrun SondereggerPhilipp ReinThomas WinderStefan BeerAlexander VonbankHeinz DrexelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17978 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Axel Muendlein Christoph H Saely Simone Geller-Rhomberg Gudrun Sonderegger Philipp Rein Thomas Winder Stefan Beer Alexander Vonbank Heinz Drexel Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
description	<h4>Background</h4>Coronary artery disease (CAD) shares common risk factors with type 2 diabetes (T2DM). Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential links between genetic variants of the TCF7L2 locus and coronary atherosclerosis are uncertain. We therefore investigated the association between TCF7L2 polymorphisms and angiographically determined CAD in diabetic and non-diabetic patients.<h4>Methodology/principal findings</h4>We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses ≥50%. Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive OR = 1.29 [1.09-1.53]; p = 0.003). This association was strong and significant in T2DM patients (n = 393; OR = 1.91 [1.32-2.75]; p = 0.001) but not in non-diabetic subjects (OR = 1.09 [0.90-1.33]; p = 0.370). The interaction risk allele by T2DM was significant (p(interaction) = 0.002), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. TCF7L2 polymorphisms rs12255372 and rs11196205 were also significantly associated with CAD in diabetic patients (adjusted additive OR = 1.90 [1.31-2.74]; p = 0.001 and OR = 1.75 [1.22-2.50]; p = 0.002, respectively). Further, haplotype analysis demonstrated that haplotypes including the rare alleles of all investigated variants were significantly associated with CAD in the whole cohort as well as in diabetic subjects (OR = 1.22 [1.04-1.43]; p = 0.013 and OR = 1.67 [1.19-2.22]; p = 0.003, respectively).<h4>Conclusions/significance</h4>These results suggest that TCF7L2 variants rs7903146 rs12255372, and rs11196205 are significantly associated with angiographically diagnosed CAD, specifically in patients with T2DM. TCF7L2 therefore appears as a genetic link between diabetes and atherosclerosis.
format	article
author	Axel Muendlein Christoph H Saely Simone Geller-Rhomberg Gudrun Sonderegger Philipp Rein Thomas Winder Stefan Beer Alexander Vonbank Heinz Drexel
author_facet	Axel Muendlein Christoph H Saely Simone Geller-Rhomberg Gudrun Sonderegger Philipp Rein Thomas Winder Stefan Beer Alexander Vonbank Heinz Drexel
author_sort	Axel Muendlein
title	Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
title_short	Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
title_full	Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
title_fullStr	Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
title_full_unstemmed	Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
title_sort	single nucleotide polymorphisms of tcf7l2 are linked to diabetic coronary atherosclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/ea521dcd5ff644ad90f0ac0f3f485a2a
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Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.

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