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Impact of a novel mutation in the 5′-flanking region of natriuretic peptide precursor B gene on the antihypertensive effects of sodium nitroprusside in patients with hypertension

Abstract

Our aim was to identify the possible mutations of the natriuretic peptide precursor B (NPPB) gene in a family with hereditary hypertension, and determine whether the mutations are associated with the antihypertensive effect of sodium nitroprusside. The subjects included one family with hereditary hypertension, 36 cases of sporadic hypertension and 120 healthy controls. The 5′-flanking sequence of NPPB was amplified with PCR, and the presence of mutations was analyzed by direct sequencing. Patients with hypertension were treated with sodium nitroprusside and blood pressure data and serum B-type natriuretic peptide (BNP) levels were measured. A novel complex mutation in 5′-flanking sequence of the NPPB gene was detected in three patients (II 2, III 2, and III 5) of the hypertension family, which included c.-1195_ -1176 insert 5′-CCTTCTTTCTTTCTTTCTTT-3′, c.-1208 T>A, c.-1214 T>C, and c.-1216 T>A. Patients with this mutation were less sensitive to sodium nitroprusside treatment. Sporadic hypertension patients (without NPPB gene mutation) and patients with the c.-1181 T>A point mutation were sensitive to sodium nitroprusside treatment. BNP levels of patients with the complex mutation were significantly lower than that of sporadic hypertension patients and c.-1181 T>A mutation patients before and during the early stage of sodium nitroprusside treatment. The complex mutation of the NPPB gene might be an etiological factor of hereditary malignant hypertension, and it is associated with low sensitivity to the antihypertensive effect of sodium nitroprusside.

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Acknowledgements

Grants covering the research: We gratefully acknowledge the financial support of the National High Technology Investigation Project Foundation of China (2008AA02Z433), the National Natural Science Foundation of China (20975021,20805006) and the Major Program Foundation of Fujian Medical University (09ZD013).

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Correspondence to C-z Lin.

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No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. The manuscript has been submitted solely to this journal and is not published, in press, or submitted elsewhere. The authors declare no conflict of interest.

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Zeng, K., Wu, Xd., Liu, Qc. et al. Impact of a novel mutation in the 5′-flanking region of natriuretic peptide precursor B gene on the antihypertensive effects of sodium nitroprusside in patients with hypertension. J Hum Hypertens 27, 271–276 (2013). https://doi.org/10.1038/jhh.2012.25

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