Endothelial function and endothelial nitric oxide synthase intron 4a/b polymorphism in primary hyperparathyroidism

Abstract

Patients with symptomatic primary hyperparathyroidism (pHT) have increased cardiovascular morbidity and mortality. Endothelial nitric oxide synthase (eNOS) intron 4a/b polymorphism is associated with coronary artery disease and hypertension in various populations. Our aim is to evaluate endothelial function in patients with pHT during pre-operative hypercalcemic and post-operative normocalcemic periods and to determine whether intron 4a/b polymorphism of eNOS gene influences endothelial function. Forty patients with pHT (age 48.48+/-11.64 yr) were examined pre-operatively and reexamined 5.8+/-1.9 months after parathyroidectomy. Forty-three healthy subjects (age 47.13+/-8.14 yr) were served as control group. Endothelial function was determined by flow-mediated dilation of brachial artery (FMD). eNOS4a/b polymorphism was detected by polymerase chain reaction. FMD was significantly lower in patients pre-operatively compared with controls (8.48+/-1.78% vs 19.49+/-2.34%, p<0.001). FMD improved significantly after parathyroidectomy (16.19+/-2.16%, p<0.001 compared with pre-operative measurements), but was still significantly lower than controls (p<0.001). The distribution of eNOS4a/b genotype frequencies was not significantly different between patients and controls. Logistic regression analysis showed that increased serum calcium (>2.47 mmol/l) and PTH concentrations (>7.75 pmol/l) were significant independent predictors of lower FMD (<16.7%). ENOS4a/b polymorphism did not enter in this model. Impaired endothelial function in patients with pHT improves after successful parathyroid surgery. No compelling data are evident to suggest that eNOS4a/b polymorphism modifies the endothelial function in patients with pHT.