Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.

Methods

RAAS gene polymorphisms were determined using mutagenically separated PCR and PCR-RFLP method in a total of 270 subjects consisting of 70 hypertensive subjects without type 2 diabetes mellitus (T2DM), 60 T2DM, 65 hypertensive subjects with T2DM and 75 control subjects.

Results

There was significant difference found in age, body mass index, systolic/diastolic blood pressure, fasting plasma glucose and high density lipoprotein cholesterol levels between the hypertensive subjects with or without T2DM and control subjects. No statistically significant differences between groups were found in the allele frequency and genotype distribution for A20C variant of AGT gene, MboI of renin, Gly460Trp of aldosterone and Lys173Arg of adducin (p > 0.05). However, the results for A6G of AGT gene revealed significant differences in allele and genotype frequencies in essential hypertension with or without T2DM (p < 0.001).

Conclusion

Among the five polymorphisms of RAAS genes only A6G variant of AGT gene was significantly associated in Malaysian essential hypertensive and type 2 diabetic subjects. Therefore, A6G polymorphism of the AGT gene could be a potential genetic marker for increased susceptibility to essential hypertension with or without T2DMin Malaysian subjects.

Related collections

Most cited references 48

Record: found
Abstract: found
Article: not found

Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension.

T Azzani, L Zagato, P Manunta … (1997)

Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an alpha/beta heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an alpha-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations. Linkage analysis of three DNA markers at different distances from the alpha-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the alpha-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp alpha-adducin allele. Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9.1%, 6.5%, and 4.7%) and the significance level for linkage (p = 0.0006, p = 0.0119, and p = 0.0211) both decreased with increasing distance from the alpha-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p = 0.0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15.9 [SE 2.0] vs 7.4 [1.3] mm Hg; p = 0.001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14.7 [2.2] vs 6.8 [1.4] mm Hg; p = 0.002). Our findings of significant linkage of the alpha-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that alpha-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the alpha-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium.

0 comments Cited 64 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.

R Puryear, J Lalouel, Rafael T Nakajima … (1997)

In earlier studies, we provided statistical evidence that individual differences in the angiotensinogen gene, the precursor of the vasoactive hormone angiotensin II, constitute inherited predispositions to essential hypertension in humans. We have now identified a common variant in the proximal promoter, the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder. Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleotide substitution affects the basal transcription rate of the gene. These observations provide some biological insight about the possible mechanism of a genetic predisposition to essential hypertension; they may also have important evolutionary implications.

0 comments Cited 56 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Prevalence, awareness, treatment and control of hypertension in Malaysia: a national study of 16,440 subjects.

L Rampal, S. Rampal, M Azhar … (2008)

A cross-sectional study was conducted in all states of Malaysia to determine the prevalence, awareness, treatment and control of hypertension. A stratified two-stage cluster sampling design with proportional allocation was used. Trained nurses obtained two blood pressure measurements from each subject. Hypertension was defined as mean systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg, or a self-reported diagnosis of hypertension and taking antihypertensive medication. All data were analysed using Stata 9.2 software and took the complex survey design into account. A two-sided P-value of <0.05 was considered to be statistically significant. The overall prevalence of hypertension for subjects aged 15 years was 27.8% (95% confidence interval (CI) 26.9-28.8). The prevalence of hypertension was significantly higher in males (29.6%, 95% CI 28.3-31.0) compared with females (26.0%, 95% CI 25.0-27.1). Multivariate logistic regression showed that the odds of having hypertension increased with increasing age, in males, in subjects with a family history of hypertension, with increasing body mass index, in non-smokers and with decreasing levels of education. Only 34.6% of the subjects with hypertension were aware of their hypertensive status, and 32.4 were taking antihypertensive medication. Amongst the latter group, only 26.8% had their blood pressure under control. The prevalence of hypertension amongst those aged 30 years has increased from 32.9% in 1996 to 40.5% in 2004. In Malaysia, the prevalence of hypertension is high, but levels of awareness, treatment and control are low. There is an urgent need for a comprehensive integrated population-based intervention programme to ameliorate the growing problem of hypertension in Malaysians.

0 comments Cited 54 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cardiovasc Diabetol

Title: Cardiovascular Diabetology

Publisher: BioMed Central

ISSN (Electronic): 1475-2840

Publication date Collection: 2009

Publication date (Electronic): 25 February 2009

Volume: 8

Page: 11

Affiliations

[1 ]Genetic Research Group, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia

[2 ]Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia

Article

Publisher ID: 1475-2840-8-11

DOI: 10.1186/1475-2840-8-11

PMC ID: 2656464

PubMed ID: 19243623

SO-VID: d51d21c3-b300-435d-8b15-149fa8119ff1

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Analysis of renin-angiotensin aldosterone system gene polymorphisms in malaysian essential hypertensive and type 2 diabetic subjects

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

Journal of the ASEAN Federation of Endocrine Societies

Most cited references 48

Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension.

A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.

Prevalence, awareness, treatment and control of hypertension in Malaysia: a national study of 16,440 subjects.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 308

Cited by 12

Most referenced authors 1,188