Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth.
OBJECTIVE
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.
Zhu
Haidong
H
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912-3710, USA. hzhu@mail.mcg.edu
Wang
Xiaoling
X
Dong
Yanbin
Y
Treiber
Frank A
FA
Snieder
Harold
H
D000367:Age Factors; D000483:Alleles; D044383:Black People; D001794:Blood Pressure; D003971:Diastole; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006352:Heart Ventricles / Q000473:pathology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000473:pathology*; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012306:Risk; D012737:Sex Factors; D013599:Systole; D044465:White People; D001741:Black or African American
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III