Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth

Pharmacogenet Genomics. 2005 Sep;15(9):669-75. doi: 10.1097/01.fpc.0000172244.65417.7a.

Abstract

Objectives: To evaluate the impact of the endothelial nitric oxide synthase (eNOS) gene on longitudinal development of blood pressure (BP) and left ventricular mass (LVM) from childhood into early adulthood.

Methods: Three polymorphisms including -922A>G, intron 4VNTR, and Glu298Asp of the eNOS gene were investigated. Individual growth-curve modeling and haplotype trend regression analyses were conducted for 579 white and black American youths with 12 assessments over a 15-year period.

Results: Significantly different allele and genotype frequencies were observed between blacks and whites for all three polymorphisms. Linkage disequilibrium (LD) patterns among these polymorphisms were also different between ethnic groups: strong LD between the -922A>G and intron 4 VNTR loci was observed in whites but not in blacks. Single locus analyses identified a significant interaction between the intron 4 VNTR and gender on diastolic BP (DBP) levels. The 4a allele carriers had significantly lower DBP levels in males (P=0.012), but higher DBP levels in females (P=0.045). Haplotype analyses confirmed the DBP lowering effect in males (P=0.049). DBP in males homozygous for haplotype G-4a-Glu was 2.58 mmHg lower than males homozygous for the most common haplotype (A-non4a-Glu). Additionally, individuals homozygous for haplotype G-non4a-Glu showed a 0.51 mmHg steeper increase in DBP per year with age as compared to the most common haplotype (P=0.007). No associations between single polymorphisms or haplotypes of the eNOS gene and systolic BP or LVM were found.

Conclusions: our results suggest that eNOS gene may have gender-specific and age-dependent effects on DBP and the development of hypertension risk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Alleles
  • Black People
  • Blood Pressure
  • Diastole
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Heart Ventricles / pathology*
  • Heterozygote
  • Homozygote
  • Humans
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / pathology*
  • Introns
  • Linkage Disequilibrium
  • Male
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Polymorphism, Genetic
  • Regression Analysis
  • Risk
  • Sex Factors
  • Systole
  • White People

Substances

  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III