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Influence of the ECE1b C‐338A polymorphism on plasma levels of ET‐1, NOx, and blood pressure
Author(s) -
Fenty NM,
Ellis TJ,
Roth SM,
Hickey M,
Brown MD
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1229-a
Subject(s) - medicine , nox , endothelin 1 , genotype , endothelin receptor , blood pressure , endocrinology , chemistry , polymorphism (computer science) , genotyping , biology , biochemistry , gene , organic chemistry , combustion , receptor
Endothelin converting enzyme‐1 (ECE‐1) is the main protease responsible for endothelin‐1 (ET‐1) generation. The ECE‐1b isoform of the ECE‐1b gene may impact vascular ET‐1 generation, nitric oxide (NO) availability and blood pressure (BP) regulation. Recently, a C to A substitution in the promoter at position −338 was shown to be associated with higher BP levels and increased promoter activity. We hypothesized that the ECE‐1b −338A allele would be associated with higher ET‐1 and BP levels, and lower NO metabolites (NOx) in pre‐ and stage 1 hypertensives. Forty‐seven 59±0.9yr old, sedentary men and women were recruited. Blood samples were collected after >12hr fast. Casual BP was measured on three separate occasions and averaged. Plasma ET‐1 and NOx levels were determined by colorimetric assays. Genotyping was done by standard PCR methods. Statistical analyses were performed using ANCOVA with adjustments for gender and ethnicity. Though no differences reached statistical significance, the AA genotype group had higher ET‐1 levels, (AA, 5.3±0.7, CA, 5.04±0.7, CC, 4.13±0.8 pg/ml); lower NOx levels (AA, 16.1±1.1, CA, 18.0±1.12, CC, 20.0±1.8 μM); and higher systolic and diastolic BP (AA, 137±3/90±2; CA, 131±3/87±2; CC, 130±3/87±2 mmHg) compared to the CA and CC groups. These preliminary findings suggest that the AA genotype may contribute to the pathogenesis of hypertension via higher ET‐1 levels and lower NO bioavailability, which may lead to endothelial dysfunction and increased vascular resistance.