Eur J Endocrinol
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DOI: 10.1530/EJE-07-0704
European Journal of Endocrinology, Vol 158, Issue 5, 615-622
Copyright © 2008 by European Society of Endocrinology
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CLINICAL STUDIES

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

Fatma Sen1, Mustafa Demirturk1, Neslihan Abaci2, Ebru Golcuk3, Huseyin Oflaz3, Ali Elitok3, Faruk Kutluturk, Halim Issever4, Nihan Erginel Unaltuna2 and Nese Colak Ozbey

Division of Endocrinology, Department of Medicine, Istanbul Faculty of Medicine, Istanbul University, 34390 Capa, Istanbul, Turkey1 Department of Medicine, Istanbul Faculty of Medicine2 Department of Genetics, Institute for Experimental Medical Research, Istanbul University, 34390 Istanbul, Turkey, Departments of3 , Cardiology4 Public Health, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey

(Correspondence should be addressed to N C Ozbey; Email: nozbey{at}hotmail.com)

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≥45 years, and BMI≥27.9 kg/m2 were significant independent predictors of IMT≥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.






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