A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes

Li, Yanna; Jain, Sudhir; Patil, Sai; Kumar, Ashok

doi:10.1016/j.vph.2005.09.009

Cited by 4 publications

(4 citation statements)

References 39 publications

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“…Similar results on the association of haplotype 235T and -6A variants were reported by Wang et al, 24 while a study by Brand et al 75 reported -6A allele to be in complete LD with T235 allele and that it is associated with higher AGT expression in vitro. Li et al 76 reported that an increased expression of the AGT gene containing haplotype AAT in the liver and adipocytes may be a contributing factor for hypertension. Further, a study data involving African Americans suggested that the AGT haplotypes containing -217A, -532T, -793A and -1074T may be involved in increased transcription of the AGT gene and may play a role in human hypertension.…”

Section: Discussionmentioning

confidence: 99%

Estimation of risk and interaction of single nucleotide polymorphisms at angiotensinogen locus causing susceptibility to essential hypertension: a case control study

Charita

Gunda

Sushma

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Introduction:The risk conferred by the variants and haplotypes of single nucleotide polymorphisms (SNPs) at human angiotensinogen (AGT) gene to essential hypertension (EHT) have been described in several populations with variations in the results attributed to their ethnicity. We attempted to evaluate the risk of -217G>A, -152G>A, -20A>C, -6G>A, T174M, M235T and 15241A>G polymorphisms at AGT locus along with the analyses of haplotype and epistatic interactions in causing susceptibility to EHT. Method: Two-hundred and forty-nine hypertensives and 248 controls were genotyped for the selected markers. Results: Study of demographic parameters revealed significant association of obesity, positive family history and nonvegetarian diet habit, suggesting elevated risk of the condition when associated with these parameters. Significantly high risk for males with AA genotype of -217G>A polymorphism was observed for developing EHT (p = .07). Males with -217A (p = .01) showed a two-fold higher risk for EHT. Markers -217G>A and -6G>A were in strong linkage disequilibrium in patients as compared to controls. Strong epistatic interactions were found between -6G>A, M235T and -217G>A markers, supporting the synergistic effect between them leading to EHT. Conclusion: Our findings suggest that -217A variant is significantly associated with the risk for EHT in males. Further studies on the functional role of the marker -217 are recommended for understanding the cause of association with EHT. KeywordsEssential hypertension (EHT), angiotensinogen (AGT), linkage disequilibrium (LD), multifactor dimensionality reduction (MDR), single nucleotide polymorphism (SNP), haplotype association, epistatic interaction, statistical package for social sciences (SPSS)

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Section: Discussionmentioning

confidence: 99%

Estimation of risk and interaction of single nucleotide polymorphisms at angiotensinogen locus causing susceptibility to essential hypertension: a case control study

Charita

Gunda

Sushma

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…In the 2.1-kilobase pair sequence of the angiotensinogen promoter, the haplotype A (-217) T (-532) A (-793) T (-1074, ATAT) was found to increase promoter activity on transient transfection in preadipocytes and differentiated adipocytes compared with the GCGG haplotype [10]. The variant -217A has been suggested to associate with hypertension in African Americans [11].…”

Section: Adipocytes As a Source Of Ras Components: Relationship To Hymentioning

confidence: 99%

Local adipose tissue renin-angiotensin system

Cassis

Yiannikouris²,

Thatcher

2008

Current Science Inc

193

148

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A local renin-angiotensin system (RAS) has been proposed in adipocytes. Adipocytes are a suggested source of components of the RAS, with regulation of their production related to obesity-hypertension. Both angiotensin type 1 and 2 receptors have been localized to adipocytes. Angiotensin II has been demonstrated to regulate adipocyte growth and differentiation, lipid metabolism, and expression and release of adipokines and RAS components, and to promote oxidative stress. Differences in regional expression of RAS components in visceral versus subcutaneous adipose tissue have been suggested as a link between abdominal obesity and cardiovascular disease. Finally, several studies support antihypertensive efficacy of RAS blockade in patients with type 2 diabetes and obesity. Future studies should address the role of adipocyte-specific deficiency of RAS components to definitively determine the relevance of the adipose RAS to normal physiology and to the development of hypertension.

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“…Li et al found that the haplotype AAT (constructed by -532T, -793A, and -1074T) almost occurring with -217A has increased promoter activity of AGT gene. 29 Dickson et al illustrated that the -20 and -217 polymorphisms have large influence on the AGT transcription. 103 Indeed, the A/G polymorphism at -217 (rs5049) could affect the promoter activity of the human AGT gene, thereby being associated with EH.…”

Section: Discussionmentioning

confidence: 99%

“…14 In 1992, it was firstly reported that the AGT polymorphisms were involved with the risk of hyper-tension in the populations of Utah and France. 13 Since then, the associations between these polymorphisms and the risk of EH had been extensively studied in the populations of Caucasians, 15 –20 African Caribbeans, 21 Mexican populations, 22–26 African Americans, 16,18,27–34 European Americans, 27,33 Europeans, 35–39 Japanese, 40–44 Indians, 45 –53 pure Malays, 54 Mongolians, 55 Australians, 56 Brazilians, 57 Saudi Arabians, 58 Africans, 59 Caucasians, 59 Turks, 60 Iranians, 61 Dutch, 62 Asians, 20,39,59,63 Chinese, 64…”

Section: Introductionmentioning

confidence: 99%

Risk given byAGTpolymorphisms in inducing susceptibility to essential hypertension among isolated populations from a remote region of China: A case-control study among the isolated populations

Sun

et al. 2015

J Renin Angiotensin Aldosterone Syst

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Introduction: Hypertension is a serious risk factor affecting up to 30% of the world's population with a heritability of more than 30-50%. The aim of this study was to investigate the contribution of the polymorphisms localized in the angiotensinogen (AGT) gene, a main component of the renin-angiotensin-aldosterone system, in inducing the susceptibility to essential hypertension (EH) among isolated populations (Yi and Hani minorities) with low prevalence rate from the remote region of Yunnan in China. Methods: A case-control association study was performed, and all subjects were genotyped for the seven single nucleotide polymorphisms localized in the AGT region by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: Three polymorphisms, i.e. rs5046, rs5049, and rs2478544, were significantly associated with EH among the Hani minority. The associations, found in the Yi minority, did not reach a conclusive level of statistical significance. The polymorphisms of rs2478544 and rs5046 caused the transformations of exonic splicing enhancer sites and transcription factor binding sites, respectively, in the bioinformatic analyses. The haplotype-rs5046T, rs5049A, rs11568020G, rs3789679C, rs2478544C was susceptible for EH among the Hani minority. Conclusion: Our findings suggested that the AGT polymorphisms have played a vital role in determining an individual's susceptibility to EH among the isolated population, which would be helpful for EH management in the remote mountainous region of Yunnan in China.

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A haplotype of angiotensinogen gene that is associated with essential hypertension increases its promoter activity in adipocytes

Cited by 4 publications

References 39 publications

Estimation of risk and interaction of single nucleotide polymorphisms at angiotensinogen locus causing susceptibility to essential hypertension: a case control study

Estimation of risk and interaction of single nucleotide polymorphisms at angiotensinogen locus causing susceptibility to essential hypertension: a case control study

Local adipose tissue renin-angiotensin system

Risk given byAGTpolymorphisms in inducing susceptibility to essential hypertension among isolated populations from a remote region of China: A case-control study among the isolated populations

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