Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants

J. E. Tanus-Santos, M. Desai, D. A. Flockhart

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated inconsistently with cardiovascular diseases. A maldistribution of eNOS variants among ethnic groups may explain interethnic differences in nitric oxide (NO)-mediated vasodilation and response to drugs. To test this possibility, we examined the distribution of genetic variants of three clinically relevant eNOS polymorphisms (T-786C in the promoter, the variable number of tandem repeats (VNTR) in intron 4, and the Glu298Asp variant in exon 7) in 305 ethnically well-characterized DNA samples (100 Caucasians, 100 African-Americans, and 105 Asians). We estimated the haplotype frequency, and evaluated associations between these variants. The Asp298 variant was more common in Caucasians (34.5%) than in African-Americans (15.5%) or Asians (8.6%)(P <0.0001). The C-786 variant was also more common in Caucasians (42.0%) than in African-Americans (17.5%) or Asians (13.8%) (P <0.0001). The 4a variant in intron 4 was more common in African-Americans (26.5%) than in Caucasians (16.0%) or Asians (12.9%) (P <0.0001). The most common predicted haplotype in the three groups combined only wild-type variants. Asians had the highest frequency of this haplotype (77% in Asians v. 46% in the other groups). In Caucasians, the Asp298 and C-786 variants were associated, and this haplotype was predicted to have a frequency of 24%. In African-Americans, the second most common haplotype included the variant 4a and wild-type variants; the Asp298 and 4a variants were associated negatively in this group. The C-786 and 4a variants were associated in Asians (P <0.0001). The marked interethnic differences that we found in the distribution of eNOS variants, in the estimated haplotype frequency, and in the association between variants may help us to understand how the combination of these genetic variants may influence cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)719-725
Number of pages7
JournalPharmacogenetics
Volume11
Issue number8
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Nitric Oxide
Haplotypes
African Americans
Nitric Oxide Synthase Type III
Introns
Cardiovascular Diseases
Minisatellite Repeats
Ethnic Groups
Vasodilation
Exons
DNA
Pharmaceutical Preparations
Genes

Keywords

  • Endothelial nitric oxide synthase
  • Genotype
  • Interethnic differences
  • Polymorphism

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. / Tanus-Santos, J. E.; Desai, M.; Flockhart, D. A.

In: Pharmacogenetics, Vol. 11, No. 8, 2001, p. 719-725.

Research output: Contribution to journalArticle

Tanus-Santos, J. E. ; Desai, M. ; Flockhart, D. A. / Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. In: Pharmacogenetics. 2001 ; Vol. 11, No. 8. pp. 719-725.
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abstract = "Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated inconsistently with cardiovascular diseases. A maldistribution of eNOS variants among ethnic groups may explain interethnic differences in nitric oxide (NO)-mediated vasodilation and response to drugs. To test this possibility, we examined the distribution of genetic variants of three clinically relevant eNOS polymorphisms (T-786C in the promoter, the variable number of tandem repeats (VNTR) in intron 4, and the Glu298Asp variant in exon 7) in 305 ethnically well-characterized DNA samples (100 Caucasians, 100 African-Americans, and 105 Asians). We estimated the haplotype frequency, and evaluated associations between these variants. The Asp298 variant was more common in Caucasians (34.5{\%}) than in African-Americans (15.5{\%}) or Asians (8.6{\%})(P <0.0001). The C-786 variant was also more common in Caucasians (42.0{\%}) than in African-Americans (17.5{\%}) or Asians (13.8{\%}) (P <0.0001). The 4a variant in intron 4 was more common in African-Americans (26.5{\%}) than in Caucasians (16.0{\%}) or Asians (12.9{\%}) (P <0.0001). The most common predicted haplotype in the three groups combined only wild-type variants. Asians had the highest frequency of this haplotype (77{\%} in Asians v. 46{\%} in the other groups). In Caucasians, the Asp298 and C-786 variants were associated, and this haplotype was predicted to have a frequency of 24{\%}. In African-Americans, the second most common haplotype included the variant 4a and wild-type variants; the Asp298 and 4a variants were associated negatively in this group. The C-786 and 4a variants were associated in Asians (P <0.0001). The marked interethnic differences that we found in the distribution of eNOS variants, in the estimated haplotype frequency, and in the association between variants may help us to understand how the combination of these genetic variants may influence cardiovascular diseases.",
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AB - Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated inconsistently with cardiovascular diseases. A maldistribution of eNOS variants among ethnic groups may explain interethnic differences in nitric oxide (NO)-mediated vasodilation and response to drugs. To test this possibility, we examined the distribution of genetic variants of three clinically relevant eNOS polymorphisms (T-786C in the promoter, the variable number of tandem repeats (VNTR) in intron 4, and the Glu298Asp variant in exon 7) in 305 ethnically well-characterized DNA samples (100 Caucasians, 100 African-Americans, and 105 Asians). We estimated the haplotype frequency, and evaluated associations between these variants. The Asp298 variant was more common in Caucasians (34.5%) than in African-Americans (15.5%) or Asians (8.6%)(P <0.0001). The C-786 variant was also more common in Caucasians (42.0%) than in African-Americans (17.5%) or Asians (13.8%) (P <0.0001). The 4a variant in intron 4 was more common in African-Americans (26.5%) than in Caucasians (16.0%) or Asians (12.9%) (P <0.0001). The most common predicted haplotype in the three groups combined only wild-type variants. Asians had the highest frequency of this haplotype (77% in Asians v. 46% in the other groups). In Caucasians, the Asp298 and C-786 variants were associated, and this haplotype was predicted to have a frequency of 24%. In African-Americans, the second most common haplotype included the variant 4a and wild-type variants; the Asp298 and 4a variants were associated negatively in this group. The C-786 and 4a variants were associated in Asians (P <0.0001). The marked interethnic differences that we found in the distribution of eNOS variants, in the estimated haplotype frequency, and in the association between variants may help us to understand how the combination of these genetic variants may influence cardiovascular diseases.

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