The G???217A variant of the angiotensinogen gene affects basal transcription and is associated with hypertension in a Taiwanese population

Wu, Shengxi; Chiang, Fu-Tien; Jiang, Jun-Ran; Hsu, Kwan-Lih; Chern, Tser-Haw; Tseng, Yung‐Zu

doi:10.1097/00004872-200311000-00015

Cited by 20 publications

(17 citation statements)

References 31 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: 92%

“…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: 92%

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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“…Our result on significant association of AA genotype (tested under the recessive model) and allele A at -217 with EHT is in accordance with the reports of Wu et al, 50,67 while it is in contrast to the finding of Jain et al, 49 who reported a significant association of AA genotype and allele A with hypertension in the dominant model.…”

Section: Discussionsupporting

confidence: 91%

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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“…On the basis of our results from a transcriptional activity study of the AGT gene, we found that a more upstream promoter region, in addition to the core-promoter element 1 that contains the A-20C and G-6A polymorphisms, 21 also plays a critical role in transcriptional control. 22 Therefore, we also chose the G-152A and G-217A polymorphisms in this upstream region for the present study.…”

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confidence: 99%

Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation

et al. 2004

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Background-The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. Methods and Results-A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected.The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls ( 2 ϭ62.5, Pϭ0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (Pϭ0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. Conclusions-This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.

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The G???217A variant of the angiotensinogen gene affects basal transcription and is associated with hypertension in a Taiwanese population

Abstract: Our study showed a significant association between the -217A variant of the AGT gene and hypertension. This variant plays a functional role in basal transcription of AGT, and may confer a risk for hypertension in Taiwanese populations.

Cited by 20 publications

References 31 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

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

Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation

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