Universität zu Köln

Pfister, R., Barnes, D., Luben, R. N., Khaw, K. -T., Wareham, N. J. and Langenberg, C. (2011). Individual and cumulative effect of type 2 diabetes genetic susceptibility variants on risk of coronary heart disease. Diabetologia, 54 (9). S. 2283 - 2288. NEW YORK: SPRINGER. ISSN 1432-0428

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Abstract

Type 2 diabetes is a major risk factor for CHD. We hypothesised that diabetes genetic susceptibility variants might be associated with increased CHD risk. We examined the individual and cumulative effect of 38 common genetic variants previously reported to be associated with type 2 diabetes on risk of incident CHD in 20,467 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk Study who had been free of CHD at baseline. During a mean follow-up of 10.7 years, 2,190 participants had a CHD event. Two individual variants next to the TSPAN8 (HR 1.07, 95% CI 1.00-1.14) and the CDKN2A/B region (1.11, 1.04-1.17) were significantly associated with increased CHD risk. A genetic score based on the 38 diabetes variants was significantly associated with an increased risk of CHD (1.08, 1.01-1.14 per score tertile). Adjustment for prevalent and incident diabetes attenuated the association of the TSPAN8 variant (1.06, 0.99-1.13) and the genetic score (1.05, 0.99-1.12 per score tertile) with CHD risk, but not that of the CDKN2A/B variant (1.11, 1.05-1.18). Addition of the genetic score did not improve risk discrimination based on clinical risk factors. The increased risk of CHD observed with genetic susceptibility to type 2 diabetes was at least partly mediated by its diabetes-predisposing effect and was not useful for clinical risk discrimination. The potential role of pathways associated with the variant CDKN2A/B in linking diabetes and CHD needs further exploration.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pfister, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barnes, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Luben, R. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Khaw, K. -T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wareham, N. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langenberg, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-490256
DOI:	10.1007/s00125-011-2206-5
Journal or Publication Title:	Diabetologia
Volume:	54
Number:	9
Page Range:	S. 2283 - 2288
Date:	2011
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0428
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ARTERY-DISEASE; ASSOCIATION; LOCUS Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49025