OBJECTIVES: To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension. METHODS: Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected. RESULTS: The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01). CONCLUSIONS Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.
Humans ; Middle Aged ; Aged ; Reactive Oxygen Species ; Essential Hypertension/genetics* ; Adenosine Triphosphate ; Cell Line ; Mutation

This study aimed to investigate the differential expression profiles of microRNAs (miRNAs) in peripheral blood lymphocytes between patients with essential hypertension and healthy individuals in Xinjiang Kazakh and to provide insight into the mechanism involved in the pathogenesis of hypertension in this ethnic group. From April 2016 to May 2019, 30 Kazakh patients with essential hypertension in the inpatient and outpatient departments of Cardiology, First Affiliated Hospital of Shihezi University were used as the hypertension group; 30 healthy Kazakh patients were used as the control group. The miRNA expression profiles in peripheral blood lymphocytes of 6 Kazakh hypertensive patients and 6 matched healthy individuals were compared, and the differentially expressed miRNAs were analyzed by cluster analysis, GSEA enrichment analysis, target gene prediction, target gene annotation and other bioinformatics analyses. In addition, qRT-PCR was used to verify the differentially expressed miRNAs. The results showed that compared with the control group, 73 differentially expressed miRNAs were identified in the hypertension group, of which 39 miRNAs were up-regulated and 34 miRNAs were down-regulated. A total of 11 miRNAs related to hypertension were screened by GSEA enrichment analysis, including hsa-miR-100-5p, hsa-miR-150-5p, hsa-miR-299-5p, hsa-miR-299-3p, hsa-miR-296-5p, hsa-miR-196b-5p, hsa-miR-503-5p, hsa-miR-628-5p, hsa-miR-874-3p, hsa-miR-543 and hsa-miR-940. qRT-PCR test found that the expression of hsa-miR-100-5p, hsa-miR-299-5p, hsa-miR-299-3p, hsa-miR-196b-5p, hsa-miR-503-5p, hsa-miR-628-5p and hsa-miR-543 was up-regulated, while the expression of hsa-miR-150-5p, hsa-miR-296-5p, hsa-miR-874-3p and hsa-miR-940 was down-regulated in the hypertension group compared with the control group. The expression trend in the gene chip was consistent with the results verified by qRT-PCR. Using online database to predict target genes of 11 miRNAs related to hypertension, we found that a total of 1 647 target genes might be regulated by these 11 miRNAs. GO function enrichment showed that (a) in biological processes, the predicted hypertension related target genes are mainly relevant to nervous system development, cellular localization, regulation of cellular metabolic process, generation of neurons and positive regulation of biological process; (b) In terms of cellular components, they are mainly related to membrane-bounded organelle, cytoplasm, intracellular membrane-bounded organelle, synapse part, neuron part, and nucleoplasm; (c) In terms of molecular function, they are mainly related to protein binding, transcription regulatory region DNA binding, RNA polymerase II regulatory region DNA binding, transcription regulator activity, and ion binding. KEGG enrichment analysis showed that the p53 signaling pathway, adrenergic signaling in cardiomyocytes, cAMP signaling pathway, TGF-β signaling pathway, endocrine and other factor-regulated calcium reabsorption, mTOR signaling pathway, and aldosterone-regulated sodium reabsorption may be related to the occurrence and development of hypertension. In conclusion, there are significant differences in the expression of miRNAs in peripheral blood lymphocytes between Kazakh patients with essential hypertension and healthy people. The differentially expressed miRNAs may be related to the occurrence and development of essential hypertension in Kazakh. However, the underlying mechanism needs to be further explored and verified.
Humans ; Computational Biology ; Essential Hypertension ; Gene Expression Profiling ; MicroRNAs/genetics* ; Lymphocytes ; China ; DNA

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of STK39 gene with response to hydrochlorothiazide among ethnic Han Chinese patients with essential hypertension. METHODS: In total 118 patients with essential hypertension were recruited. All participants had received six weeks of treatment with hydrochlorothiazide 25 mg daily. Blood pressure (BP) and heart rate (HR) were measurement every 2 weeks. Genotypes of STK39 rs3754777 and rs6749447 were determined using a SNaPshot technique. RESULTS: A significant difference was found in ΔSBP between individuals with rs3754777 CC, CT and TT and those with rs3754777 CC and CT-TT (P<0.05). A significant difference was also detected in ΔDBP between those with rs3754777 CC and CT-TT (P<0.05). No significant difference was found in ΔSBP and ΔDBP between individuals with STK39 rs6749447 GG, GT and TT (all P>0.05). Relative risk analysis showed that STK39 rs3754777 was significantly associated with BP response to hydrochlorothiazide (OR=0.416, 95%CI=0.189-0.918, P<0.05). CONCLUSION Polymorphisms of STK39 rs3754777 may be associated with BP response to hydrochlorothiazide among ethnic Han Chinese with essential hypertension.
Asian Continental Ancestry Group ; Essential Hypertension ; Genotype ; Humans ; Hydrochlorothiazide ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics

BACKGROUNDAldehyde dehydrogenase 2 (ALDH2) is involved in the pathophysiological processes of cardiovascular diseases. Recent studies showed that mutant ALDH2 could increase oxidative stress and is a susceptible factor for hypertension. In addition, wild-type ALDH2 could improve the endothelial functions, therefore reducing the risk of developing atherosclerosis. The aim of the present study was to explore the frequency of the Glu504Lys polymorphism of the ALDH2 gene and its relation to carotid intima-media thickness (CIMT) in a group of patients with essential hypertension (EH) and to investigate the association between the Glu504Lys polymorphism and CIMT in Chinese Han patients with EH.

METHODSIn this study, 410 Chinese Han patients with EH who received physical examinations at the People's Hospital of Sichuan Province (China) were selected. DNA microarray chip was used for the genotyping of the Glu504Lys polymorphism of the ALDH2 gene. The differences in CIMT among patients with different Glu504Lys ALDH2 genotypes were analyzed.

RESULTSThe mean CIMT of the patients carrying AA/AG and GG genotypes was 1.02 ± 0.31 mm and 0.78 ± 0.28 mm, respectively. One-way ANOVA showed that the CIMT of the patients carrying the AA/AG genotype was significantly higher than in the ones carrying the GG genotype (P < 0.001). Multivariate logistic regression showed that the Glu504Lys AA/AG genotype of the ALDH2 gene was one of the major factors influencing the CIMT in patients with EH (odds ratio = 3.731, 95% confidence interval = 1.589-8.124, P = 0.001).

CONCLUSIONSThe Glu504Lys polymorphism of the ALDH2 gene is associated with the CIMT of Chinese Han patients with EH in Sichuan, China.

Adult ; Aged ; Aldehyde Dehydrogenase, Mitochondrial ; genetics ; Asian Continental Ancestry Group ; Carotid Intima-Media Thickness ; China ; Essential Hypertension ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; genetics ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; genetics ; Risk Factors

BACKGROUNDG-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.

METHODSA total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.

RESULTSBaseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.

CONCLUSIONThe GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.

Adult ; Aged ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Benzimidazoles ; therapeutic use ; Benzoates ; therapeutic use ; Blood Pressure ; drug effects ; Essential Hypertension ; Female ; Genotype ; Heterotrimeric GTP-Binding Proteins ; genetics ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; genetics

OBJECTIVETo assess the association of plasma homocysteine (Hcy) level and 66A/G and 524C/T polymorphisms of methionine synthase reductase (MSR) gene with essential hypertension (EH) in ethnic Uygurs and Hans from Xinjiang.

METHODSFrom September 2011 to July 2014, 199 Uyghur and 216 Han patients were collected, while 195 healthy Uyghur ethnics and 217 healthy Han ethnics were recruited as the controls. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RELP) was adopted to detect the above polymorphisms. Enzyme immunological assay was applied to measure the levels of plasma Hcy.

RESULTSCompared with the control, plasma Hcy levels were significantly higher in EH group in both Uyghur and Han ethnics (P<0.05). In both ethnic groups, there were also significant differences in MSR 524C/T polymorphism between the patients and controls (Uyghur: chi-square=6.559, P=0.038; Han: chi-square=12.684, P=0.002). No significant difference was found in MSR 66A/G polymorphism between the patients and controls in both ethnic groups (P>0.05). Plasma Hcy level in those with a 66G/524C genotype was statistically higher than that with 66A/524T (P<0.05). After adjusting confounding factors such as gender and age, Logistic regression analysis indicated that age (OR=1.924, 95% CI:1.177- 3.164, P=0.009), obesity (OR=2.491, 95% CI: 1.584-3.920, P<0.01), hyperhomocysteine (OR=1.609, 95% CI: 1.016-2.548, P=0.043) were independent risk factors for EH in Uygurs, while age (OR=1.133, 95% CI: 1.010-81.272, P=0.033), hyperhomocysteine level (OR=3.894, 95% CI: 2.432-6.237, P<0.01), and obesity (OR=1.864, 95% CI: 1.141-3.046, P=0.013) were independent risk factors for EH in Han ethnics. No association was found between the polymorphisms and EH in Uygurs and Hans.

CONCLUSIONAge, hyperhomocysteine and obesity were common independent risk factors for EH in both Uygur and Han ethnics from Xinjiang. The MSR 66G genotype can increase the plasma concentration of Hcy, while MSR 524T genotype may reduce it. MSR 524C/T TT genotype may be a protective factor for EH. MSR polymorphisms 66A/G and 524C/T are not independent risk factors for EH in Uygur and Han ethnics from Xinjiang.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Essential Hypertension ; Female ; Ferredoxin-NADP Reductase ; genetics ; metabolism ; Homocysteine ; blood ; Humans ; Hypertension ; blood ; enzymology ; ethnology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Elucidate the mechanism of Eucommiae Cortex in treatment of hypertension, to provide the basis for further research and development of Eucommiae Cortex. Our study using the entity grammar systems inference rules to analyse the interactions of chemical constituents of Eucommiae Cortex and disease target proteins at the molecular level, and got a biological network of Eucommiae Cortex anti-hypertension which inciude 602 nodes and 2 354 edges. We got 3 treatment of hypertension pathways of Eucommiae Cortex by analyzing biological network, that is, by inhibition of vascular remodeling to improve the deterioration of hypertension, reduce activity of polymorphism genetic genes related to essential hypertension, inhibition of carbonic anhydrase 1 to maintain the osmotic pressure, Eucommiae Cortex play the role of anti-hypertension.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Essential Hypertension ; Eucommiaceae ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; Signal Transduction ; drug effects

OBJECTIVETo investigate the cystathione beta synthase (CBS) gene T833C, G919A, 844ins68 polymorphisms and plasma homocysteine (Hcy) levels in ethnic Uyghur and Han patients with essential hypertension (EH) in Xinjiang.

METHODSFour hundred twenty nine cases including 211 Uyghur and 218 Han EH patients were recruited, whilst 410 healthy individuals including 210 Uyghurs and 200 Hans were used as the controls. Amplification refractory mutation system (ARMS) was adopted to analyze the CBS gene polymorphisms including T833C, G919A and 844ins68. Enzymoimmunoassay was applied to determine the plasma level of Hcy. Chemiluminescence was applied to determine the plasma folic acid and vitamin B12.

RESULTSCompared with the controls, the plasma Hcy level was significantly higher in the EH group in both ethnic Uyghurs and Hans (P < 0.05). Plasma levels of Hcy in T833C, G919A genotypes (for both heterozygotes and homozygotes) were statistically higher than wild types (P < 0.05). A significant difference was detected in G919A polymorphism between the EH patients and controls in both Uyghur and [CM(144.5mm] Han ethnics (Uyghur: x² = 10.264, P < 0.01; Han: x² = 23.075, P < 0.01), and in T833C between the EH patients and controls in ethnic Uyghurs (x² = 40.254, P < 0.01). Logistic regression analysis indicated that age (OR=1.151, P=0.047, 95% CI = 1.002-1.323), T833C (CC) (OR = 1.078, P = 0.003, 95% CI = 1.043-1.114), obesity (OR = 1.284, P = 0.021, 95% CI = 1.038-1.590), hyperhomocysteine (OR = 3.296, P = 0.016, 95% CI = 1.244-8.733) were independent risk factors for EH among ethnic Uygurs, while age (OR = 1.162, P = 0.007, 95% CI = 1.042-1.297), obesity (OR = 3.501, P = 0.003, 95% CI = 1.521-8.060), hyperhomocysteine (OR = 1.046, P = 0.031, 95% CI = 1.011-1.459) were independent risk factors for EH in ethnic Hans after adjusting for confounding factors.

CONCLUSIONPlasma level of Hcy is associated with ethnic Uyghur and Han patients with EH in Xinjiang. CBS gene T833C CC genotype may be associated with the EH among Uyghur ethnics.

Adult ; Aged ; China ; ethnology ; Cystathionine beta-Synthase ; genetics ; Essential Hypertension ; Female ; Gene-Environment Interaction ; Homocysteine ; blood ; Humans ; Hypertension ; genetics ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo assess the association of tag single nucleotide polymorphisms (tag SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from Yunnan, China.

METHODSA case-control study was carried out. Four tag SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients with essential hypertension and 312 healthy controls using polymerase chain reaction - restriction fragment length polymorphism(PCR-RFLP) method.

RESULTSNo significant difference in genotypic and allelic distributions of the four polymorphisms was detected between the two groups(P>0.05), and the same results existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype constructed with rs1956921 and rs5244 were greater in male patients compared with male controls(P<0.01).

CONCLUSIONThe rs1956921 C allele of the CMA1 gene and the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for essential hypertension in ethnic Yi males from Yunnan.

Adult ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Pressure ; China ; ethnology ; Chymases ; genetics ; Essential Hypertension ; Female ; Humans ; Hypertension ; ethnology ; genetics ; physiopathology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo assess the association of polymorphisms of G protein-coupled inwardly-rectifying potassium channels 4 (GIRK4) gene with essential hypertension in ethnic Uygurs from southern Xinjiang.

METHODSA total of 1194 (461 males and 733 females) Uygur residents aged 30 to 70 and with a body mass index (BMI) over 18.5 kg/m(2) were selected from Hetian region. All of the subjects have received questionnaire survey, physical examination, biochemical analysis and blood pressure measurement. They were divided into hypertensive group and normotensive group. Genotyping by the TaqMan polymerase chain reaction method was performed for 4 common single nucleotide polymorphisms (rs4937391, rs2604204, rs6590357 and rs1122149), and a case-control study was carried out.

RESULTSGenotype distributions of rs4937391, rs2604204, rs6590357 and rs1122149 in both groups were in Hardy-Weinberg equilibrium (P> 0.05). The average systolic blood pressure of CC genotype of rs11221497 single nucleotide polymorphism (SNP)[(132.69± 26.9) mmHg)] was higher than the CG genotype [(127.4± 22.7) mmHg] and GG genotype [(121.1± 26.3) mmHg]. There has a significantly difference in average systolic and diastolic blood pressures between CC and GG genotypes (P< 0.05). A case-control association analysis revealed that the rs11221497 SNP was in association with essential hypertension with the dominant model [P< 0.05, OR= 0.67 (0.49-0.93)]. Haplotype analysis indicated that H6(C-G-C-G) was significantly more common in normotensive group than hypertensive group (P= 0.001).

CONCLUSIONThe rs11221497 SNP of the GIRK4 gene is associated with essential hypertension in ethnic Uygur population in Xinjiang.

Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Essential Hypertension ; Female ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; genetics ; Genetic Predisposition to Disease ; Humans ; Hypertension ; complications ; genetics ; Male ; Obesity ; complications ; genetics ; Polymorphism, Single Nucleotide