Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives

Brand-Herrmann, Stefan-Martin; Köpke, Karla; Reichenberger, Florian; Schmidt-Petersen, Klaus; Reineke, Thomas; Paul, Martin; Zidek, Walter; Brand, Eva

doi:10.1097/01.hjh.0000125429.28861.58

Cited by 29 publications

(17 citation statements)

References 33 publications

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“…As an association has been identified between the common variant of M235 T in the AGT gene and EH occurrence, 2 several studies were performed in an effort to identify other genetic polymorphisms which may influence BP. [13][14][15][16] A community-based study showed that the T174 M and M235 T polymorphisms were associated with the onset of EH in Japanese, especially in those consuming high-salt diet, 15 and this was consistent with the findings from our current study.…”

Section: Discussionsupporting

confidence: 82%

“…9,10,13,14 Several functional studies have indicated that AGT A-6G, A-20C and G-217A polymorphisms in the promoter region play important roles in regulating the AGT gene transcription and expression. [17][18][19] In a recent study, Dickson et al 10 further testified the hypothesis that the polymorphisms in the AGT promoter may affect cell function, specifically regulation in the level of AGT transcription in AGT-producing tissues.…”

Section: Discussionmentioning

confidence: 99%

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Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

Jiang

Sheng

et al. 2008

J Hum Hypertens

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Renin-angiotensin (RAS) genes, a group of promising candidate genes involved in essential hypertension (EH), play a key role in blood pressure regulation. Recently, a series of novel RAS gene polymorphisms were reported, which significantly influence the rate of the gene transcription. This study was designed to explore the association between the RAS gene polymorphisms and EH in a remote countryside population. We examined six polymorphisms in the main component genes of RAS: angiotensin-converting enzyme (ACE) (I/D), angiotensinogen (AGT) (A-6G, A-20C, G-217A and T174 M) and angiotensin type 1 receptor (AT1R) (A1166C). Six polymorphisms were genotyped by gene chip technology. Association studies were performed in 220 EH patients and 235 normotensives.Our results revealed that AGT A-6G, T174 M and ACE-I/D were significantly associated with EH (AGT A-6G: AG þ GG vs AA; OR ¼ 1.36; 95% CI ¼ 1.04-1.77. T174M: CT þ TT vs CC; OR ¼ 1.45; 95% CI ¼ 1.15-1.90. ACE I/D: ID þ DD vs II; OR ¼ 1.171; 95% CI ¼ 1.00-1.37). Moreover the logistic regression analysis suggested that the haplotype of AGT À6A, 174C, À217G and À20A might decrease the risk of EH (OR ¼ 0.64; 95% CI ¼ 0.49-0.83), after adjusting the confounding factors of gender, age and BMI. In conclusion, the AGT A-6G, T174 M and ACE I/D polymorphisms are associated with EH and the AGT haplotype À6A, 174C, À217G and À20A decrease the risk of EH in the southern Chinese population.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

Jiang

Sheng

et al. 2008

J Hum Hypertens

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“…15,16 Haplotypes were predicted using the programme PHASE (version 2.1), which implements a Bayesian method for estimating haplotypes from population genotype data. [17][18][19] A two-tailed P-value less than 0.05 was considered statistically significant. With the study sample size, there was 95% power to detect an odds ratio of 2.5 for a minor allele with a frequency greater than 0.1.…”

Section: Discussionmentioning

confidence: 99%

Association of hypertension with single nucleotide polymorphisms in the quantitative trait locus for abdominal obesity-metabolic syndrome on chromosome 17

et al. 2006

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Genome scan in Chinese revealed an association of blood pressure with the microsatellite marker D17S1303, which lies in a quantitative trait locus for the abdominal obesity-metabolic syndrome (AOMS2) at 17p12 on chromosome 17. We previously reported that D17S1303 was associated with hypertension and obesity. Therefore, we studied 10 single nucleotide polymorphisms (SNP) within 3 kb of D17S1303. One hundred and eighty hypertensive subjects (91 men, 89 women, age 53712 years) and 180 normotensive matched controls (91 men, 89 women, age 52711) were genotyped using the Sequenom genotyping platform. Allelic frequencies in these Chinese subjects differed from those reported for Caucasians. Three SNPs (rs11656507, rs1357926, rs852319) were homozygous in our subjects. The genotype frequencies of rs852320, rs852321 and rs852322 did not differ between hypertensive and normotensive subjects. However, there were significant differences for rs1525402 (P ¼ 0.048), rs2692343 (P ¼ 0.022), rs2692344 (P ¼ 0.017) and rs2321313 (P ¼ 0.028). A four-locus haplotype comprising G at rs1525402, C at rs2692343, C at rs2692344 and G at rs2321313 was associated with lower systolic blood pressure (P ¼ 0.023) and normotension (P ¼ 0.048). Our results provide further evidence that there is a gene, as yet unidentified, influencing blood pressure in the vicinity of D17S1303 in a quantitative trait locus for abdominal obesity-metabolic syndrome at 17p12.

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“…Transfection studies have revealed that A-20C mutation in the AGT promoter leads to higher AGT transcription. Therefore, A-20C mutation may lead to changes in plasma AGT levels [5,11]. Thus, we hypothesized that AGT A-20C mutation could lead to an increase in BP.…”

Section: Discussionmentioning

confidence: 99%

“…Understanding the disease in terms of molecular genetics may assist in preventing and diagnosing EH and enhancing the effectiveness of drug therapy. Aside from its roles in the renin angiotensin system in regulating salt metabolism, vascular permeability and sympathetic nervous system activity, AGT also plays an important role in the pathogenesis of hypertension [5,6]. Studies have focused on searching for the relationship between AGT polymorphism and susceptibility to hypertension [7,8].…”

Section: Discussionmentioning

confidence: 99%

Epidemiological Study of AGT Gene Polymorphism among Chinese Subjects with Primary Hypertension

Zhang¹,

Yang²,

Cui³

et al. 2012

Adv Pharmacoepidem Drug Safety

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Background: Polymorphisms in the promoter region of the angiotensinogen (AGT) gene may affect AGT transcription and thus blood pressure. We determined the frequency of the AGT A-20C polymorphism in Chinese patients with primary hypertension. Using a molecular epidemiology approach, we also determined the relationship between primary hypertension and environmental-AGT A-20C polymorphism interactions.Methods: 912 subjects diagnosed with primary hypertension were analyzed from Shenyang Chinese Populations and their samples were genotyped using A-20C polymorphism within angiotensinogen (AGT) gene by estriction ragment ength Polymorphism methods (PCR-RFLP)Results: PCR and restriction fragment length polymorphism techniques were used to determine the distribution frequency of AGT A-20C alleles. Frequencies of 84.7% and 15.3% were observed for the A and C alleles, respectively. The polymorphism was in Hardy-Weinberg equilibrium according to a χ 2 test (χ 2 =0.58, P>0.05). Linear regression of AGT genotype and blood pressure revealed that systolic blood pressure was significantly higher for AC and CC genotypes compared to the wild-type AA genotype in females (P<0.05). Conclusion:This is the first report on the frequency of AGT A-20C polymorphism in a Chinese population. Compared to the AA genotype, the effects of genotypes AC and CC on blood pressure were mainly manifest as significantly higher systolic blood pressure in females.

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Angiotensinogen promoter haplotypes are associated with blood pressure in untreated hypertensives

Abstract: Our results designate the C-532T and G-6A as the best candidates for functional studies on the AGT gene. Haplotype-based analyses should greatly aid in the dissection of the genetic basis of complex traits, such as BP regulation and hypertension.

Cited by 29 publications

References 33 publications

Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

Association of hypertension with single nucleotide polymorphisms in the quantitative trait locus for abdominal obesity-metabolic syndrome on chromosome 17

Epidemiological Study of AGT Gene Polymorphism among Chinese Subjects with Primary Hypertension

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