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(Hypertension. 2004;44:884.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Endothelin-1 Gene and Progression of Blood Pressure and Left Ventricular Mass

Longitudinal Findings in Youth

Yanbin Dong; Xiaoling Wang; Haidong Zhu; Frank A. Treiber; Harold Snieder

From the Georgia Prevention Institute Department of Pediatrics (Y.D., X.W., H.Z., F.A.T., H.S.) and Department of Psychiatry (F.A.T.), Medical College of Georgia, Augusta; and Twin Research and Genetic Epidemiology Unit (H.S.), St. Thomas’ Hospital, London, UK.

Reprint requests to Dr Yanbin Dong Georgia Prevention Institute, Medical College of Georgia, 1120 15th St, Building HS-1640, Augusta, GA 30912-3710. E-mail ydong{at}mcg.edu

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.

Key Words: endothelin • polymorphisms • haplotypes

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