1.MicroRNA and left ventricular hypertrophy.
Lian DUAN ; Xing-jiang XIONG ; Yong-mei LIU ; Jie WANG
China Journal of Chinese Materia Medica 2014;39(17):3211-3215
MicroRNAs (miRNA) plays an important role in biological development and disease occurrence and development, and acts as a "main switch" in biology. Among patients of essential hypertension, around 1/3 would suffer left ventricular hypertrophy (LVH). Hence, essential hypertension becomes an independent risk factor for cardiovascular diseases. And miRNAs plays an important role in the occurrence and development of LVH. This paper reviewed the role of miRNA in regulating the stress signaling pathway, defined its impact on the occurrence of LVH, and further emphasized the opportunities and challenges of miRNA as a biomarker and therapeutic target.
Essential Hypertension
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Humans
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Hypertension
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complications
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genetics
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Hypertrophy, Left Ventricular
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complications
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genetics
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MicroRNAs
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genetics
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Risk Factors
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Signal Transduction
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genetics
2.Bioinformatics analysis of the microRNA expression profile in the peripheral blood lymphocytes of Kazakh patients with essential hypertension in Xinjiang.
Yan WANG ; Liang ZHANG ; Rui YANG ; Li-Ya SHAN ; Lu WANG ; Ying-Ying ZHANG ; Xin-Zhi LI ; Ke-Tao MA
Acta Physiologica Sinica 2022;74(5):751-762
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
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Computational Biology
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Essential Hypertension
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Gene Expression Profiling
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MicroRNAs/genetics*
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Lymphocytes
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China
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DNA
3.Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation.
Yunfan HE ; Wenxu LI ; Zhen LIU ; Juanjuan ZHANG ; Minxin GUAN
Journal of Zhejiang University. Medical sciences 2023;52(4):510-517
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
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Middle Aged
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Aged
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Reactive Oxygen Species
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Essential Hypertension/genetics*
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Adenosine Triphosphate
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Cell Line
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Mutation
4.Meta analysis on the association of CYP11B2 gene polymorphism and essential hypertension in Chinese Han population.
Wen-jing YE ; Ling ZHENG ; Zheng-hua WANG ; Huan-huan CHEN
Chinese Journal of Cardiology 2013;41(9):795-799
OBJECTIVETo explore the association between CYP11B2 gene polymorphism and essential hypertension, blood pressure level in Chinese Han population by meta-analysis.
METHODSAfter searching database, the research quality was quantified according to NOS. Genetic model, heterogeneity, publication bias, overall OR/standardized mean difference (SMD) and 95%CI were explored by Stata, 19 studies including 9249 subjects were included in this meta-analysis.
RESULTSCompared to control group, OR(95%CI) of CC vs. TT, CT vs. TT, CC vs. CT in essential hypertensive patients were 1.022(95%CI: 0.879-1.190), 1.108 (95%CI: 0.951-1.291), 1.050(95%CI:0.995-1.109), respectively; SMD (95%CI) was 0.315 (0.066-0.565, P < 0.05) for systolic pressure derived CC vs. TT, and 0.088 (0.014-0.162, P < 0.05) for CT vs.
TT CONCLUSIONIndividuals with -344C CYP11B2 allele are at higher risk of increased systolic blood pressure, but there is no evidence showing association between CYP11B2 polymorphism and susceptibility of essential hypertension in Chinese Han population.
Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Essential Hypertension ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; genetics ; Polymorphism, Single Nucleotide
5.Association of CMA1 gene tag single nucleotide polymorphisms with essential hypertension in Yi population from Yunnan.
Yanrui WU ; Qian LI ; Ke YANG ; Chunjie XIAO
Chinese Journal of Medical Genetics 2014;31(4):449-454
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
6.Association of STK39 gene polymorphism with response to hydrochlorothiazide among ethnic Han Chinese with essential hypertension.
Wenjing HOU ; Min LIU ; Shuhua YU ; Xiaofei WANG ; Hongyang DU ; Lijuan ZHOU ; Wei CAO
Chinese Journal of Medical Genetics 2019;36(6):639-644
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
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Essential Hypertension
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Genotype
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Humans
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Hydrochlorothiazide
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Polymorphism, Single Nucleotide
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Protein-Serine-Threonine Kinases
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genetics
7.Association of cystathionine β-synthase gene polymorphisms with essential hypertension in ethnic Uyghurs and Hans from Xinjiang.
Qingping SHI ; Ying ZHANG ; Hong WANG ; Juyan OUYANG ; Fang CHEN ; Meng XU
Chinese Journal of Medical Genetics 2015;32(1):94-100
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
8.Association between polymorphism of ATP2B1 gene, its interaction with smoking and essential hypertension -a case-control study.
Juanjuan SONG ; Haiying ZHANG ; Hongbo ZHOU ; Tianxiao LI ; Ying DENG
Chinese Journal of Epidemiology 2014;35(5):588-592
OBJECTIVETo investigate the association between polymorphism of ATP2B1 gene, its interaction with smoking and susceptibility of essential hypertension.
METHODSA case-control study was conducted to elucidate the role of ATP2B1 gene variants related to the risk of essential hypertension. Genomic DNA was extracted from peripheral blood leukocytes, using the QIAamp DNA Mini Kit (QIAGEN,Germany). Two SNPs, - rs17249754 and rs6253, were examined on 1 280 patients and 1 010 healthy controls, using a Snapshot method. Statistical analyses were performed with SPSS Windows software (version 19.0;SPSS, Chicago, IL).
RESULTSA significant difference was found in rs17249754 allele frequency between cases and controls (OR = 1.223, 95%CI: 1.083-1.381, P = 0.001). After adjustment for age, sex, BMI, smoking and drinking, the difference was still statistically significant (OR = 1.212, 95%CI:1.070-1.373, P = 0.003). In addition, data from genotype distribution analysis under different models showed that appeared significant associations between ATP2B1 gene polymorphism and essential hypertension (additive model OR = 1.469, 95%CI: 1.121-1.925, P = 0.005; dominant model OR = 1.324, 95%CI:1.029-1.704, P = 0.029;recessive model OR = 1.123, 95%CI:1.031-1.223, P = 0.008). In this study, the proportion of smokers in cases was significantly higher than that in controls (P = 0.005), but no associations between rs17249754-smoking interaction and essential hypertension were found after the adjustment for gender, age, BMI and alcohol consumption (OR = 1.024, 95% CI:0.614-1.707).
CONCLUSIONOur research findings showed that the polymorphism of ATP2B1 gene rs17249754 was significantly associated with the incidence of essential hypertension in Han population of northeastern China. However, the interaction between rs17249754 and smoking did not seem to have contributed to the occurrence of the essential hypertension.
Aged ; Case-Control Studies ; Essential Hypertension ; Female ; Humans ; Hypertension ; etiology ; Male ; Middle Aged ; Plasma Membrane Calcium-Transporting ATPases ; genetics ; Polymorphism, Single Nucleotide ; Smoking
9.Association study of PRDM16 gene polymorphisms with essential hypertension in Xinjiang Uygur population.
Nan-fang LI ; Hong-mei WANG ; Yun-wei BI ; Ling ZHOU ; Xiao-guang YAO ; Zhi-tao YAN ; Fei-ya ZU
Chinese Journal of Medical Genetics 2013;30(6):716-720
OBJECTIVETo assess the association of polymorphisms of PR domain containing 16 gene (PRDM16) with essential hypertension in ethnic Uygur population from Xinjiang, China.
METHODSFunctional regions of the PRDM16 gene were sequenced in 48 Uygur subjects with essential hypertension selected from 480 hypertensive patients and 819 normotensive controls. Representative variations were genotyped with TaqMan-PCR method. Association of variations of PRDM16 gene with hypertension was analyzed.
RESULTSFor the 4 genotyped representative variations (rs2236518, rs2282198, rs2493292 and rs870171), no significant difference in genotype distribution and allele frequencies has been found between the patient and control groups (P>0.05). By ANOVA analysis, none of the polymorphisms was significantly associated with systolic or diastolic blood pressure (P>0.05). Nor was significant difference in haplotypic frequencies between the two groups detected (P>0.05).
CONCLUSIONWe have found no association between the four polymorphisms (rs2236518, rs2282198, rs2493292 and rs870171) of the PRDM16 gene with essential hypertension in ethnic Uygur population from Xinjiang.
Asian Continental Ancestry Group ; genetics ; Blood Pressure ; genetics ; DNA-Binding Proteins ; genetics ; Essential Hypertension ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Transcription Factors ; genetics
10.Association of GIRK4 gene polymorphisms with essential hypertension in obese ethnics Uygur from southern Xinjiang.
Nanfang LI ; Hai YANG ; Delian ZHANG ; Yanrong HU ; Hongmei WANG ; Juhong ZHANG ; Xiaoguang YAO ; Jing HONG ; Ling ZHOU
Chinese Journal of Medical Genetics 2014;31(1):88-92
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