Endothelin-1 gene and progression of blood pressure and left ventricular mass: longitudinal findings in youth.
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.
Dong
Yanbin
Y
Georgia Prevention Institute Department of Pediatrics, Medical College of Georgia, Augusta 30912-3710, USA. ydong@mcg.edu
Wang
Xiaoling
X
Zhu
Haidong
H
Treiber
Frank A
FA
Snieder
Harold
H
D000293:Adolescent; D044383:Black People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D012959:Socioeconomic Factors; D044465:White People / Q000235:genetics
D019332:Endothelin-1