TY - JOUR
T1 - Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype
AU - Pitzalis, Maria Vittoria
AU - Sarzani, Riccardo
AU - Dessi-Fulgheri, Paolo
AU - Iacoviello, Massimo
AU - Forleo, Cinzia
AU - Lucarelli, Katya
AU - Pietrucci, Francesca
AU - Salvi, Fabio
AU - Sorrentino, Sandro
AU - Romito, Roberta
AU - Guida, Pietro
AU - Rappelli, Alessandro
AU - Rizzon, Paolo
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
KW - Genetics
KW - Hypertension
KW - Natriuretic peptides
KW - Receptors
KW - Risk factors
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U2 - 10.1097/00004872-200308000-00012
DO - 10.1097/00004872-200308000-00012
M3 - Article
C2 - 12872042
AN - SCOPUS:12444300095
VL - 21
SP - 1491
EP - 1496
JO - Journal of Hypertension
JF - Journal of Hypertension
SN - 0263-6352
IS - 8
ER -