Endothelin-1 gene and progression of blood pressure and left ventricular mass: Longitudinal findings in youth

Abstract

Endothelin-1 (ET-1) is a powerful vasconstrictor peptide implicated in development of essential hypertension and left ventricular hypertrophy. To evaluate the impact of genetic variability of the ET-1 gene on progression of blood pressure (BP) and left ventricular mass (LVM), we conducted individual growth curve modeling for 537 European American and black youths with 12 assessments during a 15-year period. Four common single-nucleotide polymorphisms (SNPs) including T-1370G, +138/ex1 del/ins, T-37/in2C, and Lys198Asn were included in this study. Single SNP analyses showed that individuals with the +138/ex1 ins allele had a borderline significant lower systolic BP (SBP; P=0.072). Furthermore, the -37/in2C allele showed an SBP-lowering effect in males, accounting for 1.6% between-subject variation of SBP (P=0.016). Haplotype analyses in males confirmed the BP-lowering effect of the -37/in2C allele. SBP in individuals homozygous for the del (+138/ex1) -C (-37/in2) haplotype was 3.3 mm Hg lower than those homozygous for the del (+138/ex1) -T (-37/in2) haplotype (P=0.038). For LVM, we observed a significant gene-environment interaction. LVM levels were 20 g higher in carriers versus noncarriers of the -1370G allele in the low socioeconomic status (SES) group only (P=0.004). In summary, our results uncover a sex-specific protective effect of variation in the ET-1 gene on the progression of hypertension risk, and a SES-specific effect on risk of developing left ventricular hypertrophy in multiethnic youth.