Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis

Wu, S.K.; Chiang, Fu-Tien; Chen, Wei-Jen; Liu, Pi-Hua; Hsu, Kwan Lih; Hwang, Juey‐Jen; Lai, Ling‐Ping; Lin, Jiunn Lee; Tseng, Chuen Den; Tseng, Yung Zu

doi:10.1152/physiolgenomics.00133.2003

Cited by 56 publications

(35 citation statements)

References 44 publications

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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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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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“…42 One explanation for the discrepancies could be population dependent differences in the distribution of M235T genotypes; 39 for example in several European studies, the frequency of the TT-genotype is typically between 0.1 and 0.2, 40 as in our study, while in Japanese studies reported values are around 0.7. 43 Our findings, however,…”

Section: Genetic Analysiscontrasting

confidence: 70%

Renal Haemodynamics are not Related to Genotypes in Offspring of Parents with Essential Hypertension

Skov

Madsen

Hansen

et al. 2006

J Renin Angiotensin Aldosterone Syst

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Introduction. The pathogenesis of essential hypertension (EH) has a major genetic component and is associated with renal abnormalities. Normotensive offspring of hypertensive parents are likely to develop EH and are a suitable population for identifying possible relations between genetic and renal abnormalities. Methods. We investigated if renin-angiotensin-aldosterone system associated genotypes (angiotensinogen [M235T] and ACE [I/D]) are related to blood pressure (BP), renal haemodynamics and sodium excretion in sex and age-matched (18—35 years) healthy Caucasian offspring of either two parents with EH (n=101, EH-offspring) or two normotensive parents (n=50, controls). The alpha-adducin polymorphism (G460W) was also investigated. Results. Compared to controls, BP, heart rate, renal vascular resistance (RVR) and urinary sodium excretion were, respectively, 5%, 7%, 15% and 20% higher in EH-offspring. In controls, the TT-genotype of the M235T angiotensinogen polymorphism was associated with higher BP and higher plasma angiotensinogen. By contrast, in EHoffspring the TT-genotype was associated with lower BP and unchanged plasma angiotensinogen. Plasma angiotensinogen correlated positively with BP in EH-offspring, with a similar tendency (p=0.08) in controls. The distributions of the three candidate polymorphisms were similar in EH-offspring and controls. There were no associations between any of the polymorphisms and any of the renal parameters measured. Conclusion. The markedly greater RVR, proportionally larger than the greater BP, supports a role for RVR in the pathogenesis of EH. The lack of association between the candidate polymorphisms and the investigated parameters, even in this homogenous and for hypertension strongly predisposed group, suggests that the polymorphisms investigated do not play important roles in the pathogenesis of hypertension.

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“…The angiotensin I-converting enzyme (ACE) gene has also been associated with EH in the majority of the population. In recent years, the correlation between the molecular variant of the AGT gene, M235T, and EH has started to receive attention (1)(2)(3)(4)(5)(6). AGT in the circulation is mainly synthesized in the liver.…”

Section: Introductionmentioning

confidence: 99%

Association between the M235T polymorphism of the AGT gene and cytokines in patients with hypertension

Wang

Wan

2011

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to explore the association between the M235T polymorphism of the angiotensinogen (AGT) gene and cytokines in patients with essential hypertension (EH). A total of 300 patients with EH and an agematched control group of 150 individuals without EH, secondary hypertension, myocardial infarction and diabetes were enrolled in this study. Polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP) was used to detect variation in the target genotype, and enzyme-linked immunosorbant assay (ELISA) was used to detect the cytokine [interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)] concentrations. The AGT gene 235T allele and 235TT genotype frequencies in hypertensive patients were slightly higher than those in the controls. Furthermore, in the hypertensive subjects with the AGT gene 235T allele, the concentrations of IL-1 and TNF-α were significant higher than those in the controls. The results from our study suggest that the higher AGT gene TT genotype and 235T allele frequencies may be risk factors for hypertension. High frequencies of the AGT gene 235T allele and high cytokine concentrations (IL-1 and TNF-α) may promote the transcription and expression of AGT, particularly in hypertensive patients with the 235TT genotype. IntroductionHypertension has been recognized as a significant risk factor for the development of cardiovascular diseases, including coronary heart disease (CHD), myocardial infarction (MI) and stroke, all of which are principal causes of cardiovascular morbidity and mortality in humans. Essential hypertension (EH) is a complex, polygenic disease in which numerous genes control the blood pressure level. Several candidate genes, all selected from the renin-angiotensin system-related genes, have been examined. One of the candidate genes is the gene encoding angiotensinogen (AGT), the precursor of the vasoactive peptide, angiotensin II. The angiotensin I-converting enzyme (ACE) gene has also been associated with EH in the majority of the population. In recent years, the correlation between the molecular variant of the AGT gene, M235T, and EH has started to receive attention (1-6). AGT in the circulation is mainly synthesized in the liver. The plasma AGT level mainly reflects this synthesis. It has been discovered that the expression of the AGT gene in the liver is regulated by certain cytokines. It has been reported that these cytokines [interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)] are likely to be the main activation factors in AGT gene expression. They activate the expression of the AGT gene, elevate the concentrations of AGT and ultimately accelerate the development of hypertension. In addition, IL-1 and TNF-α also induce proliferation of the smooth muscle blood vessel cells and arteriosclerosis. Studies on the association between the M235T polymorphism of the AGT gene and cytokines in hypertensive Chinese patients have been rarely reported. The aim of this study was to analyze the M235T polymorphism ...

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Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: single locus genotype vs. haplotype analysis

Cited by 56 publications

References 44 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

Renal Haemodynamics are not Related to Genotypes in Offspring of Parents with Essential Hypertension

Association between the M235T polymorphism of the AGT gene and cytokines in patients with hypertension

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