Published Online
on October 25, 2004

A more recent version of this article appeared on December 1, 2004

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Submitted on June 4, 2004
Revised on June 23, 2004

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; and 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.

^* To whom correspondence should be addressed. E-mail: ydong{at}mcg.edu.

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.

Key words: endothelin • polymorphisms • haplotypes

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