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

Valéria C. Sandrim, Juan C. Yugar-Toledo, Zeruesenay Desta, David A. Flockhart, Heitor Moreno, Jose E. Tanus-Santos

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

OBJECTIVES: Most 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. METHODS: We studied the distribution of three eNOS genetic polymorphisms: single 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. RESULTS: No 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). CONCLUSIONS: Whereas 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.

Original languageEnglish
Pages (from-to)2393-2397
Number of pages5
JournalJournal of Hypertension
Volume24
Issue number12
DOIs
StatePublished - Dec 2006

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Nitric Oxide Synthase Type III
Haplotypes
Antihypertensive Agents
Blood Pressure
Drug Therapy
Genotype
Hypertension
Minisatellite Repeats
Drug and Narcotic Control
Genetic Polymorphisms
Viperidae
Genetic Promoter Regions
Introns
Single Nucleotide Polymorphism
Exons
Arterial Pressure
Therapeutics
Alleles

Keywords

  • Endothelial nitric oxide synthase
  • Haplotypes
  • Hypertension
  • Nitric oxide
  • Polymorphisms
  • Refractory hypertension
  • Resistant hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy. / Sandrim, Valéria C.; Yugar-Toledo, Juan C.; Desta, Zeruesenay; Flockhart, David A.; Moreno, Heitor; Tanus-Santos, Jose E.

In: Journal of Hypertension, Vol. 24, No. 12, 12.2006, p. 2393-2397.

Research output: Contribution to journalArticle

Sandrim, Valéria C. ; Yugar-Toledo, Juan C. ; Desta, Zeruesenay ; Flockhart, David A. ; Moreno, Heitor ; Tanus-Santos, Jose E. / Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy. In: Journal of Hypertension. 2006 ; Vol. 24, No. 12. pp. 2393-2397.
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abstract = "OBJECTIVES: Most 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. METHODS: We studied the distribution of three eNOS genetic polymorphisms: single 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. RESULTS: No 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). CONCLUSIONS: Whereas 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.",
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T1 - Endothelial nitric oxide synthase haplotypes are related to blood pressure elevation, but not to resistance to antihypertensive drug therapy

AU - Sandrim, Valéria C.

AU - Yugar-Toledo, Juan C.

AU - Desta, Zeruesenay

AU - Flockhart, David A.

AU - Moreno, Heitor

AU - Tanus-Santos, Jose E.

PY - 2006/12

Y1 - 2006/12

N2 - OBJECTIVES: Most 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. METHODS: We studied the distribution of three eNOS genetic polymorphisms: single 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. RESULTS: No 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). CONCLUSIONS: Whereas 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.

AB - OBJECTIVES: Most 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. METHODS: We studied the distribution of three eNOS genetic polymorphisms: single 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. RESULTS: No 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). CONCLUSIONS: Whereas 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.

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KW - Haplotypes

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KW - Polymorphisms

KW - Refractory hypertension

KW - Resistant hypertension

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