Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men

Ingrid F. Metzger, Debora C. Souza-Costa, Aline S. Marroni, Sabrina Nagassaki, Zeruesenay Desta, David A. Flockhart, Jose Edwardo Tanus-Santos

Research output: Contribution to journalArticle

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Abstract

Objectives: Controversy exists regarding the effects of polymorphisms in the endothelial nitric oxide synthase (eNOS) gene on nitrites/nitrates (NO x) plasma concentrations. In this study we compared the distribution of haplotypes involving three relevant eNOS polymorphisms (T-786C in the promoter region; b/a in intron 4, and Glu298Asp in exon 7) in healthy subjects with low and high circulating NOx levels. Methods: We studied 154 healthy subjects (fasting, white males, who were non-smokers, 18-60 years of age, and not taking any medication). Genomic DNA was isolated from blood samples and genotypes were determined by PCR and restriction fragment length digestion. Circulating NOx was determined by chemiluminescence. Results: Haplotype frequencies were compared in two groups of subjects: those with the 30 lowest NOx levels (group L) and those with the 30 highest NO x levels (group H). NOx levels in group L and H were 24.2 ± 4.5 μM and 80.9 ± 8.9 μM, respectively. Genotype frequencies for the three polymorphisms were not different when the two groups were compared (all P > 0.05, chi-squared test). However, the haplotype including the alleles C (promoter), 4b (intron 4), and Glu (exon 7) was significantly more common in group L (16%) than in group H (4%) (P = 0.0047). The frequencies of the remaining haplotypes were not different among group L and H. Conclusions: While eNOS genotypes are not significantly associated with changes in the circulating NOx concentrations, the specific eNOS haplotype that includes the 'C','4b', and 'Glu' alleles is associated with lower circulating NOx concentrations.

Original languageEnglish
Pages (from-to)565-570
Number of pages6
JournalPharmacogenetics and Genomics
Volume15
Issue number8
StatePublished - Aug 2005

Fingerprint

Nitric Oxide Synthase Type III
Haplotypes
Nitric Oxide
Genes
Genotype
Introns
Exons
Healthy Volunteers
Alleles
Nitrites
Luminescence
Genetic Promoter Regions
Nitrates
Digestion
Fasting
Polymerase Chain Reaction
DNA

Keywords

  • Endothelial nitric oxide synthase
  • Genotypes
  • Haplotypes
  • Nitric oxide
  • Polymorphisms

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

Cite this

Metzger, I. F., Souza-Costa, D. C., Marroni, A. S., Nagassaki, S., Desta, Z., Flockhart, D. A., & Tanus-Santos, J. E. (2005). Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men. Pharmacogenetics and Genomics, 15(8), 565-570.

Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men. / Metzger, Ingrid F.; Souza-Costa, Debora C.; Marroni, Aline S.; Nagassaki, Sabrina; Desta, Zeruesenay; Flockhart, David A.; Tanus-Santos, Jose Edwardo.

In: Pharmacogenetics and Genomics, Vol. 15, No. 8, 08.2005, p. 565-570.

Research output: Contribution to journalArticle

Metzger, IF, Souza-Costa, DC, Marroni, AS, Nagassaki, S, Desta, Z, Flockhart, DA & Tanus-Santos, JE 2005, 'Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men', Pharmacogenetics and Genomics, vol. 15, no. 8, pp. 565-570.
Metzger, Ingrid F. ; Souza-Costa, Debora C. ; Marroni, Aline S. ; Nagassaki, Sabrina ; Desta, Zeruesenay ; Flockhart, David A. ; Tanus-Santos, Jose Edwardo. / Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men. In: Pharmacogenetics and Genomics. 2005 ; Vol. 15, No. 8. pp. 565-570.
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abstract = "Objectives: Controversy exists regarding the effects of polymorphisms in the endothelial nitric oxide synthase (eNOS) gene on nitrites/nitrates (NO x) plasma concentrations. In this study we compared the distribution of haplotypes involving three relevant eNOS polymorphisms (T-786C in the promoter region; b/a in intron 4, and Glu298Asp in exon 7) in healthy subjects with low and high circulating NOx levels. Methods: We studied 154 healthy subjects (fasting, white males, who were non-smokers, 18-60 years of age, and not taking any medication). Genomic DNA was isolated from blood samples and genotypes were determined by PCR and restriction fragment length digestion. Circulating NOx was determined by chemiluminescence. Results: Haplotype frequencies were compared in two groups of subjects: those with the 30 lowest NOx levels (group L) and those with the 30 highest NO x levels (group H). NOx levels in group L and H were 24.2 ± 4.5 μM and 80.9 ± 8.9 μM, respectively. Genotype frequencies for the three polymorphisms were not different when the two groups were compared (all P > 0.05, chi-squared test). However, the haplotype including the alleles C (promoter), 4b (intron 4), and Glu (exon 7) was significantly more common in group L (16{\%}) than in group H (4{\%}) (P = 0.0047). The frequencies of the remaining haplotypes were not different among group L and H. Conclusions: While eNOS genotypes are not significantly associated with changes in the circulating NOx concentrations, the specific eNOS haplotype that includes the 'C','4b', and 'Glu' alleles is associated with lower circulating NOx concentrations.",
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AU - Souza-Costa, Debora C.

AU - Marroni, Aline S.

AU - Nagassaki, Sabrina

AU - Desta, Zeruesenay

AU - Flockhart, David A.

AU - Tanus-Santos, Jose Edwardo

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N2 - Objectives: Controversy exists regarding the effects of polymorphisms in the endothelial nitric oxide synthase (eNOS) gene on nitrites/nitrates (NO x) plasma concentrations. In this study we compared the distribution of haplotypes involving three relevant eNOS polymorphisms (T-786C in the promoter region; b/a in intron 4, and Glu298Asp in exon 7) in healthy subjects with low and high circulating NOx levels. Methods: We studied 154 healthy subjects (fasting, white males, who were non-smokers, 18-60 years of age, and not taking any medication). Genomic DNA was isolated from blood samples and genotypes were determined by PCR and restriction fragment length digestion. Circulating NOx was determined by chemiluminescence. Results: Haplotype frequencies were compared in two groups of subjects: those with the 30 lowest NOx levels (group L) and those with the 30 highest NO x levels (group H). NOx levels in group L and H were 24.2 ± 4.5 μM and 80.9 ± 8.9 μM, respectively. Genotype frequencies for the three polymorphisms were not different when the two groups were compared (all P > 0.05, chi-squared test). However, the haplotype including the alleles C (promoter), 4b (intron 4), and Glu (exon 7) was significantly more common in group L (16%) than in group H (4%) (P = 0.0047). The frequencies of the remaining haplotypes were not different among group L and H. Conclusions: While eNOS genotypes are not significantly associated with changes in the circulating NOx concentrations, the specific eNOS haplotype that includes the 'C','4b', and 'Glu' alleles is associated with lower circulating NOx concentrations.

AB - Objectives: Controversy exists regarding the effects of polymorphisms in the endothelial nitric oxide synthase (eNOS) gene on nitrites/nitrates (NO x) plasma concentrations. In this study we compared the distribution of haplotypes involving three relevant eNOS polymorphisms (T-786C in the promoter region; b/a in intron 4, and Glu298Asp in exon 7) in healthy subjects with low and high circulating NOx levels. Methods: We studied 154 healthy subjects (fasting, white males, who were non-smokers, 18-60 years of age, and not taking any medication). Genomic DNA was isolated from blood samples and genotypes were determined by PCR and restriction fragment length digestion. Circulating NOx was determined by chemiluminescence. Results: Haplotype frequencies were compared in two groups of subjects: those with the 30 lowest NOx levels (group L) and those with the 30 highest NO x levels (group H). NOx levels in group L and H were 24.2 ± 4.5 μM and 80.9 ± 8.9 μM, respectively. Genotype frequencies for the three polymorphisms were not different when the two groups were compared (all P > 0.05, chi-squared test). However, the haplotype including the alleles C (promoter), 4b (intron 4), and Glu (exon 7) was significantly more common in group L (16%) than in group H (4%) (P = 0.0047). The frequencies of the remaining haplotypes were not different among group L and H. Conclusions: While eNOS genotypes are not significantly associated with changes in the circulating NOx concentrations, the specific eNOS haplotype that includes the 'C','4b', and 'Glu' alleles is associated with lower circulating NOx concentrations.

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