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

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 haplo-type 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.