Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy

• Published in: Journal of hypertension Vol. 24; no. 12; pp. 2393 - 2397
• Main Authors: Sandrim, Valéria C, Yugar-Toledo, Juan C, Desta, Zeruesenay, Flockhart, David A, Moreno, Heitor, Tanus-Santos, Jose E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-12-2006; Lippincott Williams & Wilkins
• Subjects: Antihypertensive agents; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Drug Resistance - genetics; Drug Resistance - physiology; Female; Haplotypes; Humans; Hypertension - drug therapy; Hypertension - enzymology; Hypertension - genetics; Male; Medical sciences; Middle Aged; Nitric Oxide Synthase Type III - genetics; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Hypertension; Treatment resistance; Enzyme; Cardiovascular disease; polymorphisms; resistant hypertension; Nitric-oxide synthase; refractory hypertension; haplotypes; Treatment; Nitric oxide; Antihypertensive agent; Arterial pressure; endothelial nitric oxide synthase; Blood pressure; Oxidoreductases; Haplotype; Polymorphism
• ISSN: 0263-6352; 1473-5598
• DOI: 10.1097/01.hjh.0000251899.47626.4f

OBJECTIVESMost hypertensive patients require two or more drugs to control arterial blood pressure effectively. Although endothelial nitric oxide synthase (eNOS) haplotypes have been associated with hypertension, it is unknown whether eNOS genotypes/haplotypes are associated with resistance to antihypertensive therapy.
METHODSWe studied the distribution of three eNOS genetic polymorphismssingle nucleotide polymorphisms in the promoter region (TC), and in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a). Genotypes were determined for 111 normotensive controls (NT), 116 hypertensive individuals who were well controlled (HT), and 100 hypertensive individuals who were resistant to conventional antihypertensive therapy (RHT). We also compared the distribution of eNOS haplotypes in the three groups of subjects.
RESULTSNo differences were found in genotype or allele distribution among the three groups (all P > 0.05). Conversely, the ‘C Glu b’ haplotype was more commonly found in the NT than in the HT or RHT groups (21 versus 8 and 7%, respectively; both P < 0.00625). In addition, the ‘C Asp b’ haplotype was more commonly found in the HT or RHT groups than in the NT group (22 and 20%, respectively, versus 8%; both P < 0.00625). The distribution of eNOS haplotypes was not significantly different in the HT and RHT groups (P > 0.05).
CONCLUSIONSWhereas our findings suggest a protective effect for the ‘C Glu b’ haplotype against hypertension and that the ‘C Asp b’ haplotype increases the susceptibility to hypertension, our results suggest that eNOS haplotypes are not associated with resistance to antihypertensive therapy.