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The Asp(298) allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus

Odeberg, Jacob; Larsson, Charlotte A LU ; Råstam, Lennart LU and Lindblad, Ulf LU (2008) In BMC Cardiovascular Disorders 8(36).
Abstract
Background: Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp(298) allele and T2DM in predisposing to acute myocardial infarction (AMI). Methods: In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp(298) allele versus the risk for AMI. Results: In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with... (More)
Background: Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp(298) allele and T2DM in predisposing to acute myocardial infarction (AMI). Methods: In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp(298) allele versus the risk for AMI. Results: In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp(298) allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in subjects without diabetes or hypertension. Compared to wild-type non-diabetic subjects, all patients with T2DM had a significantly increased risk of AMI regardless of genotype. This risk was however markedly higher in patients with T2DM homozygous for the Asp(298) allele (HR 7.20 [3.01-17.20], p < 0.001), independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL -cholesterol, current smoking, and leisure time physical activity. The pattern seemed stronger in women than in men. Conclusion: We show here a strong independent association between eNOS genotype and AMI in patients with T2DM. This suggests a synergistic effect of the eNOS Asp(298) allele and diabetes, and confirms the role of eNOS as an important pathological bottleneck for cardiovascular disease in patients with T2DM. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Cardiovascular Disorders
volume
8
issue
36
publisher
BioMed Central
external identifiers
  • wos:000266881100001
  • scopus:61349128480
ISSN
1471-2261
DOI
10.1186/1471-2261-8-36
language
English
LU publication?
yes
id
84274361-dbf2-49ef-b2d5-9e597a5cc1cd (old id 1440509)
date added to LUP
2009-07-27 14:06:38
date last changed
2017-08-13 04:05:49
@article{84274361-dbf2-49ef-b2d5-9e597a5cc1cd,
  abstract     = {Background: Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp(298) allele and T2DM in predisposing to acute myocardial infarction (AMI). Methods: In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp(298) allele versus the risk for AMI. Results: In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp(298) allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in subjects without diabetes or hypertension. Compared to wild-type non-diabetic subjects, all patients with T2DM had a significantly increased risk of AMI regardless of genotype. This risk was however markedly higher in patients with T2DM homozygous for the Asp(298) allele (HR 7.20 [3.01-17.20], p &lt; 0.001), independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL -cholesterol, current smoking, and leisure time physical activity. The pattern seemed stronger in women than in men. Conclusion: We show here a strong independent association between eNOS genotype and AMI in patients with T2DM. This suggests a synergistic effect of the eNOS Asp(298) allele and diabetes, and confirms the role of eNOS as an important pathological bottleneck for cardiovascular disease in patients with T2DM.},
  author       = {Odeberg, Jacob and Larsson, Charlotte A and Råstam, Lennart and Lindblad, Ulf},
  issn         = {1471-2261},
  language     = {eng},
  number       = {36},
  publisher    = {BioMed Central},
  series       = {BMC Cardiovascular Disorders},
  title        = {The Asp(298) allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus},
  url          = {http://dx.doi.org/10.1186/1471-2261-8-36},
  volume       = {8},
  year         = {2008},
}