OBJECTIVE: Abnormalities in the natriuretic peptide system could play a key role in the genesis of hypertension. We evaluated the associations between a family history of hypertension, cardiovascular phenotype and allelic variants of Npr1 and Npr3, two candidate genes that codify for natriuretic peptide receptors. METHODS: We genotyped 45 young normotensive subjects (19 males, 26.8 +/- 3.7 years) with accurately assessed family history of hypertension (FH+) and 52 (26 males, 26.1 +/- 3.1 years) without (FH-) for the known variants of Npr1 and Npr3 genes, and for a novel length difference (3C/4C) polymorphism at position 15129 in the 3'-untranslated region of the Npr1 gene. Blood pressure, echocardiography and plasma brain natriuretic peptide were assessed. RESULTS: Both the novel Npr1 3C allele (59 versus 33%, P < 0.001) and the 3C/3C genotype (31 versus 8%; P < 0.001) were significantly more frequent in FH+ than in FH-. The inverse distribution of the 4C/4C genotype suggested that a casual association was very unlikely. Moreover, the 3C/3C homozygous had significantly higher systolic blood pressure (121.1 +/- 6.3 versus 115.6 +/- 7.8 mmHg in 4C/4C; P < 0.05) and a longer left ventricular isovolumic relaxation time (67 +/- 10 versus 61 +/- 9 ms; P < 0.05). The Npr3 C(-55) allele variant was also more frequent in FH+ (88 versus 76%, P < 0.05), but was not associated with the cardiovascular phenotype. CONCLUSIONS: The novel Npr1 gene 3C variant and the Npr3 gene C(-55) allele are associated with hypertensive family history. Moreover, the functional Npr1 3C variant, when homozygous, is also associated with higher systolic blood pressure and prolonged ventricular relaxation.
OBJECTIVE: Abnormalities in the natriuretic peptide system could play a key role in the genesis of hypertension. We evaluated the associations between a family history of hypertension, cardiovascular phenotype and allelic variants of Npr1 and Npr3, two candidate genes that codify for natriuretic peptide receptors. METHODS: We genotyped 45 young normotensive subjects (19 males, 26.8 +/- 3.7 years) with accurately assessed family history of hypertension (FH+) and 52 (26 males, 26.1 +/- 3.1 years) without (FH-) for the known variants of Npr1 and Npr3 genes, and for a novel length difference (3C/4C) polymorphism at position 15129 in the 3'-untranslated region of the Npr1 gene. Blood pressure, echocardiography and plasma brain natriuretic peptide were assessed. RESULTS: Both the novel Npr1 3C allele (59 versus 33%, P < 0.001) and the 3C/3C genotype (31 versus 8%; P < 0.001) were significantly more frequent in FH+ than in FH-. The inverse distribution of the 4C/4C genotype suggested that a casual association was very unlikely. Moreover, the 3C/3C homozygous had significantly higher systolic blood pressure (121.1 +/- 6.3 versus 115.6 +/- 7.8 mmHg in 4C/4C; P < 0.05) and a longer left ventricular isovolumic relaxation time (67 +/- 10 versus 61 +/- 9 ms; P < 0.05). The Npr3 C(-55) allele variant was also more frequent in FH+ (88 versus 76%, P < 0.05), but was not associated with the cardiovascular phenotype. CONCLUSIONS: The novel Npr1 gene 3C variant and the Npr3 gene C(-55) allele are associated with hypertensive family history. Moreover, the functional Npr1 3C variant, when homozygous, is also associated with higher systolic blood pressure and prolonged ventricular relaxation.
Authors: Xiaofeng Zhu; J H Young; Ervin Fox; Brendan J Keating; Nora Franceschini; Sunjung Kang; Bamidele Tayo; Adebowale Adeyemo; Yun V Sun; Yali Li; Alanna Morrison; Christopher Newton-Cheh; Kiang Liu; Santhi K Ganesh; Abdullah Kutlar; Ramachandran S Vasan; Albert Dreisbach; Sharon Wyatt; Joseph Polak; Walter Palmas; Solomon Musani; Herman Taylor; Richard Fabsitz; Raymond R Townsend; Daniel Dries; Joseph Glessner; Charleston W K Chiang; Thomas Mosley; Sharon Kardia; David Curb; Joel N Hirschhorn; Charles Rotimi; Alexander Reiner; Charles Eaton; Jerome I Rotter; Richard S Cooper; Susan Redline; Aravinda Chakravarti; Daniel Levy Journal: Hum Mol Genet Date: 2011-03-21 Impact factor: 6.150
Authors: Amanda A Fox; Charles D Collard; Stanton K Shernan; Christine E Seidman; Jonathan G Seidman; Kuang-Yu Liu; Jochen D Muehlschlegel; Tjorvi E Perry; Sary F Aranki; Christoph Lange; Daniel S Herman; Thomas Meitinger; Peter Lichtner; Simon C Body Journal: Anesthesiology Date: 2009-04 Impact factor: 7.892
Authors: Peter R Sinnaeve; Mark P Donahue; Peter Grass; David Seo; Jacky Vonderscher; Salah-Dine Chibout; William E Kraus; Michael Sketch; Charlotte Nelson; Geoffrey S Ginsburg; Pascal J Goldschmidt-Clermont; Christopher B Granger Journal: PLoS One Date: 2009-09-14 Impact factor: 3.240