Endothelial nitric oxide synthase intron 4a/b polymorphism and early atherosclerotic changes in hypopituitary GH-deficient adult patients.

OBJECTIVE

Endothelial nitric oxide synthase (eNOS) intron 4a/b polymorphism is associated with plasma NO concentrations and coronary artery disease/hypertension in various populations. GH deficiency in adulthood predisposes to reduced NO concentrations and premature atherosclerosis. Our aim was to determine whether intron 4a/b polymorphism of eNOS gene influences endothelial function and early atherosclerotic changes in GH-deficient hypopituitary patients.

DESIGN

Thirty-three hypopituitary GH-deficient patients on conventional replacement therapy other than GH and 43 age-, sex-, and body mass index (BMI)-matched controls were studied in this cross-sectional case-control study.

METHODS

Early atherosclerotic changes were determined by flow-mediated dilation (FMD) of brachial artery and carotid artery intima-media thickness (IMT). eNOS4a/b polymorphism was detected by PCR.

RESULTS

Hypopituitary patients had significantly higher total/low-density lipoprotein cholesterol and fat mass and lower IGF-I concentrations compared with controls. IMT was significantly higher in patients (0.777+/-0.23 vs 0.639+/-0.17 mm, P<0.01). No significant difference was observed with respect to FMD measurements. eNOS4a/b genotype frequencies were similar between patients and controls. Patients carrying 'a' allele (a/a and a/b) had significantly higher IMT compared with controls carrying 'a' allele and bb genotype (P<0.05). However, logistic regression analysis revealed that presence of hypopituitarism, age> or =45 years, and BMI> or =27.9 kg/m(2) were significant independent predictors of IMT> or =0.65 mm.

CONCLUSION

No compelling data are evident to suggest that eNOS4a/b polymorphism modifies the atherosclerotic process in GH-deficient situations. A large case-control study is needed to confirm our findings.