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Published on: December 2, 2014

NOS3 polymorphisms are associated with arterial stiffness in children with type 1 diabetes

Issam Zineh1, Amber L Beitelshees, Michael J Haller

  • 1Department of Pharmacy Practice and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.

Diabetes Care
|March 1, 2007
PubMed

Insights

Genetic variations in the NOS3 gene are linked to arterial stiffness in children with type 1 diabetes. The -786T-->C polymorphism showed a significant association, suggesting a potential role in cardiovascular risk assessment.

Area of Science:

  • Cardiovascular Research
  • Genetics
  • Pediatric Endocrinology

Background:

  • Type 1 diabetes (T1D) is linked to endothelial dysfunction, arterial stiffness, and increased cardiovascular disease (CVD) risk.
  • Previous studies showed increased arterial stiffness in children with T1D, unexplained by traditional CVD risk factors.
  • Significant variation in arterial stiffness exists within pediatric T1D populations.

Purpose of the Study:

  • To investigate the association between NOS3 gene polymorphisms and arterial stiffness in children with T1D.
  • To explore potential genetic contributors to the variability of arterial stiffness observed in this population.

Main Methods:

  • Studied 36 children (aged 10-21) with T1D undergoing radial tonometry.
  • Measured arterial stiffness using corrected augmentation index (AI75).
  • Determined genotypes for NOS3 -786T-->C and Glu298-->Asp polymorphisms via pyrosequencing; compared AI75 values by genotype using ANOVA and multivariate analysis.

Main Results:

  • A significant difference in AI75 was found between -786TT and -786C carriers (P=0.01).
  • No significant difference in AI75 was observed between Glu298Glu and Asp298 carriers (P=0.59).
  • Univariate analysis identified age, sex, BMI percentile, and the -786T-->C genotype as significantly associated with AI75. A multivariate model including these factors was also significant (P=0.002, R2=0.40).

Conclusions:

  • This study reports the first association between the NOS3 -786T-->C polymorphism and arterial stiffness in pediatric type 1 diabetes.
  • These findings suggest a potential genetic influence on arterial stiffness in T1D.
  • Larger studies are warranted to confirm these results for potential application in CVD risk assessment.
Abstract

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