Horm Metab Res 2008; 40(1): 13-17
DOI: 10.1055/s-2007-1004527
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Endothelial NO-Synthase Intron 4 Polymorphism is Associated with Disturbed In Vivo Nitric Oxide Production in Individuals Prone to Type 2 Diabetes

K. Rittig 1 , K. Holder 1 , J. Stock 1 , O. Tschritter 1 , A. Peter 1 , N. Stefan 1 , A. Fritsche 1 , F. Machicao 1 , H-U. Häring 1 , B. Balletshofer 1
  • 1Department of Endocrinology and Diabetes, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany
Weitere Informationen


received 30.01.2007

accepted 28.06.2007

20. Dezember 2007 (online)


Insulin resistance, as well as vascular disease, both share a relevant genetic background taking the influence of a positive family history of these disorders. On the other hand, insulin resistance is associated with a proatherosclerotic disturbance in nitric oxide dependent vasodilation, probably contributing to the link between these two disorders. We examined the association between nitric oxide dependent vasodilation (measured with high resolution ultrasound at 13 MHz) and three relevant NO-synthase (eNOS)-polymorphisms in 200 insulin resistant subjects participating in the Tuebinger Lifestyle Intervention Program (TULIP). This study revealed that carriers of the eNOS intron 4 polymorphism (aa 2.16%; ab 24.2%; bb 73.2%) show significantly worse endothelial, and thereby eNOS dependent vasodilation (p=0.03, multivariate ANOVA), as compared to wildtype carriers. The 5′ UTR T-786C and the G894 T polymorphism did not show any influence on eNOS-activity. In subjects at increased risk to develop type 2 diabetes, the eNOS intron 4 polymorphism is independently associated with endothelial function as indicated by disturbed endothelial NO production. Due to the high prevalence and the relatively strong effect, this polymorphism might help to identify subjects at increased risk for atherosclerosis associated with overweight and insulin resistance.



K. Rittig, MD 

Department of Endocrinology and Diabetes

Vascular Medicine

Nephrology and Clinical Chemistry

University of Tübingen

Otfried-Müller Straße 10

72076 Tübingen


Telefon: +49/7071 29 82 71 1

Fax: +49/7071/29 44 54

eMail: kilian.rittig@med.uni-tuebingen.de