Yonsei Med J.  2015 Jan;56(1):227-234. 10.3349/ymj.2015.56.1.227.

A Polymorphism of the Renin Gene rs6682082 Is Associated with Essential Hypertension Risk and Blood Pressure Levels in Korean Women

• Park J
• Song K
• Jang Y
• Kim Yoon S

• KMID: 2352811
• DOI: http://doi.org/10.3349/ymj.2015.56.1.227

Abstract

PURPOSE
The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans.
MATERIALS AND METHODS
To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects.
RESULTS
Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4+/-0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant.
CONCLUSION
We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.

Keyword

Essential hypertension; renin; polymorphism; association

MeSH Terms

Alleles
Asian Continental Ancestry Group/*genetics
Blood Pressure/*genetics
Case-Control Studies
Diastole/genetics
Female
Gene Frequency
*Genetic Association Studies
*Genetic Predisposition to Disease
Humans
Hypertension/*genetics/*physiopathology
Luciferases/metabolism
Middle Aged
Polymorphism, Single Nucleotide/*genetics
Promoter Regions, Genetic/genetics
Renin/*genetics
Republic of Korea
Risk Factors
Systole/genetics
Transfection
Luciferases
Renin

Figure

• 

  Fig. 1 Differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by rs6682082 genotype in postmenopausal EH patients. (A) Means of SBP were 168.05±2.95 mm Hg in participants with the AA/AG genotype and 160.57±1.50 mm Hg in participants with the GG genotype (p=0.003). (B) Means of DBP were 105.32±2.37 mm Hg in participants with the AA/AG genotype and 100.39±1.14 mm Hg in participants with the GG genotype (p=0.017). BP was described by mean±standard error. EH, essential hypertension.

• 

  Fig. 2 Luciferase activity of AS 4.1 cells transfected with renin SNP rs6682082/luciferase gene constructs. The G (A) promoter construct was prepared by site-directed mutagenesis of the G allele promoter construct. The relative luciferase activity is presented by mean±standard error. *A allele vs. G allele, †G (A) allele vs. G allele. SNP, single-nucleotide polymorphism.

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