Association of NPR3 polymorphism with risk of essential hypertension in a Chinese population

D-B Kuang; J-P Zhou; M-P Li; J Tang; X-P Chen

doi:10.1111/jcpt.12549

Association of NPR3 polymorphism with risk of essential hypertension in a Chinese population

J Clin Pharm Ther. 2017 Oct;42(5):554-560. doi: 10.1111/jcpt.12549. Epub 2017 May 11.

Authors

D-B Kuang^{1

2}, J-P Zhou^{1

3}, M-P Li^{1

2}, J Tang^{1

2}, X-P Chen^{1

2}

Affiliations

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
³ Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.

PMID: 28497617
DOI: 10.1111/jcpt.12549

Abstract

What is known and objective: Essential hypertension (EH) is a common disease exhibiting large individual difference in occurrence, development and treatment response. Genetic factors are implicated in the development and progression of EH. This study aimed to explore the association between NPR3 single nucleotide polymorphism rs2270915 (A/G, Asn521Asp) and the risk of EH in a Chinese Han population by a case-control study.

Methods: The study was a single-centre, case-control trial, in which a total of 287 EH patients and 289 age- and sex-matched healthy controls were enrolled. The inclusion criteria were as follows: Han Chinese origin, male or female patients, systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg. The healthy controls were subjects without histories of cardiovascular or cerebrovascular diseases. NPR3 rs2270915 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, primary human umbilical vein endothelial cells (HUVECs) were isolated from 19 fresh human umbilical cords and cultured. Atrial natriuretic peptide (ANP) concentration in cell medium was determined by enzyme-linked immunosorbent assay (ELISA). NPR3 mRNA expression was determined by real-time semi-quantitative PCR.

Results and discussion: No significant difference in genotype distribution of NPR3 rs2270915 polymorphism was observed between cases and controls (P>.05). Patients carrying the rs2270915 G allele showed decreased SBP, and the difference was marginal. As compared with cells carrying the rs2270915 AA genotype, those with the AG genotype showed significantly lower NPR3 mRNA expression levels (P<.05) and lower medium ANP concentration (P<.001).

What is new and conclusion: This study suggested that NPR3 rs2270915 polymorphism was associated with decreased SBP level marginally in EH patients in a Chinese Han population, and the polymorphism may function through decreasing NPR3 mRNA expression and ANP level.

Keywords: NPR3; atrial natriuretic peptide; essential hypertension; human umbilical venous endothelial cells; single nucleotide polymorphism.

MeSH terms

Aged
Aged, 80 and over
Alleles
Asian People / genetics
Atrial Natriuretic Factor / metabolism*
Blood Pressure / genetics*
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Essential Hypertension / genetics*
Female
Genetic Predisposition to Disease
Genotype
Human Umbilical Vein Endothelial Cells
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction
Receptors, Atrial Natriuretic Factor / genetics*

Substances

RNA, Messenger
Atrial Natriuretic Factor
Receptors, Atrial Natriuretic Factor
atrial natriuretic factor receptor C