PURPOSE: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. METHODS: This review was written based on the modified 3(rd) step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. RESULTS: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), α-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily β-2 (CYP11β-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), 11β-hydroxysteroid dehydrogenase type-2 (HSD 11β-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L), and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, CYP11β-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. CONCLUSION: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.
Adult ; Angiotensinogen ; Blood Pressure ; Cardiovascular Diseases ; Child ; Chronic Disease ; Cytochrome P-450 Enzyme System ; Epithelial Sodium Channels ; Genetics ; Genome-Wide Association Study ; GTP-Binding Proteins ; Humans ; Hypertension ; Obesity* ; Oxidoreductases ; Peptidyl-Dipeptidase A ; Phosphotransferases ; Polymorphism, Single Nucleotide ; Sodium ; Sodium, Dietary

OBJECTIVETo observe the effect of electroacupuncture (EA) stimulation on the expressions of angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), endothelin-1 (ET1), and endothelin A receptor (ETAR) mRNA in spontaneously hypertensive rat (SHR) aorta.

METHODSEighteen male SHRs were randomly divided into three groups, an SHR group, an SHR Baihui (DU 20) and Zusanli (ST 36) acupoint (SHR-AP) group, and an SHR non-acupoint (SHR-NAP) group, with 6 rats in each group. Six Wistar rats were used as a control. Rats in the SHR-AP group were stimulated by DU 20 and ST 36 acupoints, both of which were connected with EA. EA was handled one time every Monday, Wednesday and Friday, for total 24 times (8 weeks). SHRNAP rats were acupointed at a 15°angle flat into 0.5 cm to two points, which were 1 and 2 cm from rail tip separately. EA parameters were the same as the SHR-AP rats. SHR control rats and Wistar rats were fixed without EA. Real-time quantitative polymerase chain reaction (PCR) was used to measure AGT, AT1R, ET1, and ETAR mRNA expression in rat aorta.

RESULTSEA stimulation significantly reduced rat aorta vascular AGT, ET1, ETAR and AT1R mRNA expressions in the SHR-AP and SHR-NAP groups (P <0.01). Among these four genes, AT1R mRNA expression was significantly lower in the SHR-AP than in the SHR-NAP group (P <0.01).

CONCLUSIONEA could reduce the AT1R mRNA expression in SHR-AP rat aorta, indicating a potential mechanism for the hypotensive effects of EA.

Angiotensinogen ; genetics ; metabolism ; Animals ; Aorta ; metabolism ; physiopathology ; Blood Pressure ; Electroacupuncture ; Endothelin-1 ; genetics ; metabolism ; Gene Expression Regulation ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats, Inbred SHR ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Receptor, Endothelin A ; genetics ; metabolism

The present study was designed to test the hypothesis that a medium-term simulated microgravity can induce region-specific remodeling in large elastic arteries with their innermost smooth muscle (SM) layers being most profoundly affected. The second purpose was to examine whether these changes can be prevented by a simulated intermittent artificial gravity (IAG). The third purpose was to elucidate whether vascular local renin-angiotensin system (L-RAS) plays an important role in the regional vascular remodeling and its prevention by the gravity-based countermeasure. This study consisted of two interconnected series of in-vivo and ex-vivo experiments. In the in-vivo experiments, the tail-suspended, hindlimb unloaded rat model was used to simulate microgravity-induced cardiovascular deconditioning for 28 days (SUS group); and during the simulation period, another group was subjected to daily 1-hour dorso-ventral (-G(x)) gravitation provided by restoring to normal standing posture (S + D group). The activity of vascular L-RAS was evaluated by examining the gene and protein expression of angiotensinogen (Ao) and angiotensin II receptor type 1 (AT1R) in the arterial wall tissue. The results showed that SUS induced an increase in the media thickness of the common carotid artery due to hypertrophy of the four SM layers and a decrease in the total cross-sectional area of the nine SM layers of the abdominal aorta without significant change in its media thickness. And for both arteries, the most prominent changes were in the innermost SM layers. Immunohistochemistry and in situ hybridization revealed that SUS induced an up- and down-regulation of Ao and AT1R expression in the vessel wall of common carotid artery and abdominal aorta, respectively, which was further confirmed by Western blot analysis and real time PCR analysis. Daily 1-hour restoring to normal standing posture over 28 days fully prevented these remodeling and L-RAS changes in the large elastic arteries that might occur due to SUS alone. In the ex-vivo experiments, to elucidate the important role of transmural pressure in vascular regional remodeling and differential regulation of L-RAS activity, we established an organ culture system in which rat common carotid artery, held at in-vivo length, can be perfused and pressurized at varied flow and pressure for 7 days. In arteries perfused at a flow rate of 7.9 mL/min and pressurized at 150 mmHg, but not at 0 or 80 mmHg, for 3 days led to an augmentation of c-fibronectin (c-FN) expression, which was also more markedly expressed in the innermost SM layers, and an increase in Ang II production detected in the perfusion fluid. However, the enhanced c-FN expression and increased Ang II production that might occur due to a sustained high perfusion pressure alone were fully prevented by daily restoration to 0 or 80 mmHg for a short duration. These findings from in-vivo and ex-vivo experiments have provided evidence supporting our hypothesis that redistribution of transmural pressures might be the primary factor that initiates region-specific remodeling of arteries during microgravity and the mechanism of IAG is associated with an intermittent restoration of the transmural pressures to their normal distribution. And they also provide support to the hypothesis that L-RAS plays an important role in vascular adaptation to microgravity and its prevention by the IAG countermeasure.
Angiotensinogen ; genetics ; metabolism ; Animals ; Aorta, Abdominal ; pathology ; physiopathology ; Carotid Artery, Common ; pathology ; physiopathology ; Hindlimb Suspension ; Male ; Muscle, Smooth, Vascular ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Renin-Angiotensin System ; physiology ; Weightlessness Simulation

BACKGROUNDGenetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, the aldosterone synthase (CYP11B2) gene, C-344T, and the angiotensin II type 1 receptor (AT1R) gene, A1166C, have been shown to be associated with IgA nephropathy (IgAN) and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease (ESRD) and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD.

METHODSGenotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected.

RESULTSACE, AGT, CYP and AT1R genotype distributions were similar in patients with IgAN and in controls. Comparing patients with ESRD (IgAN-ESRD) and those without ESRD (IgAN-non ESRD), there was a significant increase only in the ACE DD genotype (P < 0.05) among the four gene polymorphisms. There was significant dominance of the male (P < 0.05), more marked hypertension (P < 0.01), proteinuria (P < 0.01) and increased serum creatinine during renal biopsy (P < 0.01) in the IgAN-ESRD group.

CONCLUSIONAmong the ACE, AGT, AT1R and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.

Adult ; Angiotensinogen ; genetics ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Glomerulonephritis, IGA ; genetics ; Humans ; Kidney Failure, Chronic ; genetics ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; genetics ; Receptor, Angiotensin, Type 1 ; genetics ; Renin-Angiotensin System ; genetics

OBJECTIVE: To investigate the relationship between T704C polymorphism of angiotensinogen (AGT) gene and cerebral hemorrhage and its impact on the levels of blood pressure in Han people in Changsha. METHODS: A total of 273 cerebral hemorrhage patients (the cerebral hemorrhage group) and 140 normal controls (the control group) were collected from Jan. 2005 to Jan. 2009. DNA was extracted from their peripheral blood samples. The polymorphism of AGT-T704C was analyzed by SNaPshot and direct DNA sequencing. The possible risk factors of cerebral hemorrhage were investigated at the same time. Each group was divided into 2 subgroups (a high blood pressure subgroup and a normal blood pressure subgroup) according to whether they had essential hypertension. Logistic regression analysis was used to detect the relationship between cerebral hemorrhage and all its possible risk factors and AGT-T704C polymorphism. RESULTS: The drinking history, coronary heart disease history, essential hypertension history, and blood levels of lipids were shown significant difference between the cerebral hemorrhage group and the control group (P<0.05). Logistic regression analysis showed that hypertension history, systolic blood pressure level, and high density lipoprotein cholesterol level were independent risk factors for cerebral hemorrhage in Han people in Changsha. The genotype C/C, C/T, and T/T frequencies of AGT-T704C polymorphism in the cerebral hemorrhage group and the control group were 0.692, 0.279, 0.029 and 0.629, 0.350, 0.021, respectively. The allele C and T frequencies of AGT-T704C polymorphism in the 2 groups were 0.832, 0.168 and 0.804, 0.196, respectively. The frequencies of all the genotypes and alleles had no significant difference between the 2 groups and their subgroups (P>0.05). CONCLUSION The polymorphism of AGT-T704C may not be associated with cerebral hemorrhage and not related to the levels of lipids and blood pressure in Han people in Changsha. Hypertension history, systolic blood pressure level, and high density lipoprotein cholesterol level are the main risk factors of cerebral hemorrhage in Han people in Changsha.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Angiotensinogen ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Cerebral Hemorrhage ; genetics ; China ; ethnology ; Female ; Genotype ; Humans ; Hypertension ; complications ; Lipoproteins, HDL ; blood ; Logistic Models ; Male ; Middle Aged ; Molecular Sequence Data ; Polymorphism, Genetic ; Risk Factors ; Young Adult

OBJECTIVETo explore the relationship between angiotensinogen (AGT) gene M235T and TCM syndrome type in essential hypertension (ET) patients.

METHODSThe gene mutation frequency of AGT M235T in 168 ET patients and 42 nomotensive (NT) subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.

RESULTSThere was a significant difference in AGT M235T gene mutation between patients of Gan-fire exuberant type and those of yin-yang deficiency type (P < 0.01), homozygote type TT appeared with higher frequency. Multivariate regression linear analysis demonstrated that the genotypes of AGT M235T was correlated with the prognosis of ET to a certain degree.

CONCLUSIONGene mutation of AGT M235T may be associated with the genesis and development of ET, and the TCM syndrome type of ET has its own intrinsic molecular biological background.

Adult ; Aged ; Angiotensinogen ; genetics ; China ; Diagnosis, Differential ; Female ; Humans ; Hypertension ; diagnosis ; genetics ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Multivariate Analysis ; Mutation ; Polymorphism, Genetic ; Syndrome

OBJECTIVETo investigate the association of polymorphism of angiotensinogen (AGT) -6G/A, -20A/C and T174M with the development of deep venous thrombosis.

METHODSOne hundred and three patients with deep venous thrombosis (DVT group) and 250 healthy subjects (control group) were recruited in the study. The polymorphisms of angiotensinogen -6G/A, -20A/C and T174M were detected by PCR-RFLP.

RESULTSThe prevalence of GA genotype of -6G/A in the DVT group was significantly higher than that in the control group(P< 0.05) and the prevalence of -20A/-6A/174T haplotype in the DVT group was lower than that in the control group(P< 0.05). There were no significant differences in the prevalence of -20A/C and T174M polymorphism.

CONCLUSIONThe GA genotypes of -6G/A may increase the development of DVT and the -20A/-6G/174T haplotype may be a risk factor of DVT. However, the -20A/-6A/174T haplotype may be a protective factor of DVT.

Adult ; Angiotensinogen ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Venous Thrombosis ; genetics

BACKGROUNDThe renin-angiotensin-aldosterone system (RAAS) is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure (BP) response to diuretic treatment in a Chinese Han ethnic population.

METHODSFifty-four patients with essential hypertension received hydrochlorothiazide (12.5 mg, once daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment.

RESULTSThe patients with angiotensinogen (AGT) -6G allele showed a greater reduction in diastolic BP (P=0.025) and mean BP (P=0.039) than those carrying AA genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes (systolic BP: P=0.030; diastolic BP: P=0.026; mean BP: P=0.003). In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes (P=0.007).

CONCLUSIONSAGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.

Aged ; Angiotensinogen ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genotype ; Humans ; Hydrochlorothiazide ; therapeutic use ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the relationship of four single nucleotide polymorphism (SNP) haplotypes in the angiotensinogen (AGT) gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China.

METHODSTotal 300 subjects were allocated into three different groups: Group 1, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four polymorphisms at position -152 (G-A), -20 (A-C), -18 (C-T), and -6 (A-G) in the promoter region of AGT.

RESULTSThe frequencies of CT genotype of AGT-18 and T allele in Group 1 (P = 0.003, P = 0.004) and Group 2 (P = 0.002, P = 0.002) were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group (P = 0.016), while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 (P = 0.003) compared with the control group, while H5 haplotype frequency which included -20C and -18T was significantly increased in Group 1 (P = 0.006) versus the control.

CONCLUSIONThe -20 (A-C) and -18 (C-T) of the AGT may play an important role in pathogenesis of primary hypertension; and -20 (A-C), -18 (C-T), and -6 (A-G) may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Hainan, China.

Angiotensinogen ; genetics ; Cerebral Infarction ; complications ; genetics ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Hypertension ; complications ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

Adult ; Angiotensinogen ; genetics ; DNA Mutational Analysis ; Female ; Genome ; Humans ; Liver Cirrhosis ; genetics ; Male ; Middle Aged ; Mutation ; Promoter Regions, Genetic