BACKGROUND: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. METHODS: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. RESULTS: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. CONCLUSION SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.
Aged ; Aged, 80 and over ; Blood Platelets ; metabolism ; Body Height ; genetics ; Cross-Sectional Studies ; Endothelium, Vascular ; physiology ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; blood ; epidemiology ; genetics ; Male ; Middle Aged ; Odds Ratio ; Platelet Count ; Polymorphism, Single Nucleotide

Risk factors for hypertension consist of lifestyle and genetic factors. Family history and twin studies have yielded heritability estimates of BP in the range of 34-67%. The most recent paper of BP GWAS has explained about 20% of the population variation of BP. An overestimation of heritability may have occurred in twin studies due to violations of shared environment assumptions, poor phenotyping practices in control cohorts, failure to account for epistasis, gene-gene and gene-environment interactions, and other non-genetic sources of phenotype modulation that are suspected to lead to underestimations of heritability in GWAS. The recommendations of hypertension guidelines in major countries consist of the following elements: weight reduction, a healthy diet, dietary sodium reduction, increasing physical activity, quitting smoking, and moderate alcohol consumption. The hypertension guidelines are mostly the same for each country or region, beyond race and culture. In this review, we summarize gene-environmental interactions associated with hypertension by describing lifestyle modifications according to the hypertension guidelines. In the era of precision medicine, clinicians who are responsible for hypertension management should consider the gene-environment interactions along with the appropriate lifestyle components toward the prevention and treatment of hypertension. We briefly reviewed the interaction of genetic and environmental factors along the constituent elements of hypertension guidelines, but a sufficient amount of evidence has not yet accumulated, and the results of genetic factors often differed in each study.
Gene-Environment Interaction ; Humans ; Hypertension ; epidemiology ; genetics ; prevention & control ; therapy ; Life Style ; Practice Guidelines as Topic ; Precision Medicine ; standards ; Risk Factors

OBJECTIVETo evaluate the association between leptin receptor gene polymorphisms and hypertension in Chinese population.

METHODSThe keywords "Hypertension", "Blood Pressure, high", "Leptin Receptor", "OB Receptor", "LEPR Protein", "CD295 Antigens", and "LEPR" were used to search the literature to identify the relevant studies for meta-analysis using software RevMan 5.0 and Stata 11.0 software.

RESULTSThirteen studies involving 3210 cases of hypertension and 1881 controls were included in the meta-analysis. Overall, a significant association was found between Gln223Arg gene polymorphism and hypertension in allele contrast and dominant genetic model (for allele contrast genetic model: OR=1.17, 95%CI=1.48-2.15, P<0.0001; for dominant model: OR=2.18, 95%CI=1.75-2.72, P<0.00001). No statistically significant correlation was found between Lys109Arg polymorphism and hypertension (for allele model: OR=1.13, 95%CI=0.84-1.51, P=0.42; for recessive genetic model: OR=0.88, 95%CI=0.33-2.32, P=0.79; for dominant genetic model: OR=1.20, 95%CI=0.85-1.71, P=0.29; for additive genetic model: OR=0.90, 95%CI=0.34-2.42, P=0.84).

CONCLUSIONThere is no significant correlation between Lys109Arg variant of LEPR gene and hypertension in Chinese population, but the Gln223Arg polymorphism is associated with hypertension in allele contrast and dominant genetic model. Chinese population with an A allele are at a high risk of developing hypertension.

Alleles ; Asian Continental Ancestry Group ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Leptin ; genetics

OBJECTIVETo construct a protein-protein interaction (PPI) network in hypertension patients with blood-stasis syndrome (BSS) by using digital gene expression (DGE) sequencing and database mining techniques.

METHODSDGE analysis based on the Solexa Genome Analyzer platform was performed on vascular endothelial cells incubated with serum of hypertension patients with BSS. The differentially expressed genes were filtered by comparing the expression levels between the different experimental groups. Then functional categories and enriched pathways of the unique genes for BSS were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) to select those in the enrichment pathways. Interologous Interaction Database (I2D) was used to construct PPI networks with the selected genes for hypertension patients with BSS. The potential candidate genes related to BSS were identified by comparing the number of relationships among genes. Confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), gene ontology (GO) analysis was used to infer the functional annotations of the potential candidate genes for BSS.

RESULTSWith gene enrichment analysis using DAVID, a list of 58 genes was chosen from the unique genes. The selected 58 genes were analyzed using I2D, and a PPI network was constructed. Based on the network analysis results, candidate genes for BSS were identified: DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2BE, H3F3B, CEBPB, SAT1 and GADD45A. Verified through qRT-PCR and analyzed by GO, the functional annotations of the potential candidate genes were explored.

CONCLUSIONCompared with previous methodologies reported in the literature, the present DGE analysis and data mining method have shown a great improvement in analyzing BSS.

Aged ; Data Mining ; methods ; Databases, Factual ; Female ; Gene Expression ; Hemostatic Disorders ; epidemiology ; genetics ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Protein Interaction Maps

OBJECTIVETo analyze the distribution of matrix metalloproteinase-3 (MMP-3) genotype and its association with the blood pressure profiles in Guangzhou rural population.

METHODSThis study was conducted among 680 rural residents aged 40-70 years (including 314 men and 366 women) from 3 villages in an rural area of Guangzhou. The blood pressures of the subjects were measured and blood samples were collected for genotype analysis using polymerase chain reaction and direct sequencing of the MMP-3 gene promoter region to detect the 5 adenines (5A)/6 adenines (6A) polymorphisms.

RESULTSThe frequencies of MMP-3 genotypes 6A/6A, 5A/5A, and 5A/6A were 82.6%, 1.8% and 15.6% among these residents, respectively. The distribution of MMP-3 genotypes and allele frequencies showed no significant gender- or age-related variations. The men with different genotypes (6A/6A vs 5A/6A+5A/5A) did not show significant differences in blood pressure levels, whereas the women with 5A/6A+5A/5A genotypes had higher systolic and diastolic blood pressures than those with a 6A/6A genotype. The allele 5A was highly frequent in the hypertensive residents as compared with the normotensive residents.

CONCLUSIONSThe 6A homozygote is the predominant genotype of MMP-3 in Guangzhou rural population, which has a significantly lower proportion of 5A homozygote than the Western populations. The 5A allele is associated with a high risk of hypertension especially in women and may affect both systolic and diastolic blood pressures.

Adult ; Age Distribution ; Aged ; Alleles ; Blood Pressure ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Matrix Metalloproteinase 3 ; genetics ; Middle Aged ; Risk Factors ; Rural Population ; Sex Distribution

PURPOSE: Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes. MATERIALS AND METHODS: We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined. RESULTS: Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02). CONCLUSION: These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.
Adiponectin/genetics ; Asian Continental Ancestry Group ; Atherosclerosis/epidemiology/genetics ; Blood Glucose/metabolism ; Cadherins/*genetics ; Cholesterol/blood ; Female ; Humans ; Hypertension/epidemiology/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics

OBJECTIVETo evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-β1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population.

METHODSThe subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension.

RESULTSThe frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05).

CONCLUSIONSNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

Aged ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics ; Receptors, Transforming Growth Factor beta ; genetics

PURPOSE: The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19*2 (681G>A) and CYP2C19*3 (636G>A) and the development of essential hypertension (EH) in Koreans. MATERIALS AND METHODS: We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot(TM) assay. RESULTS: The distribution of alleles and genotypes of CYP2C19*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19*1/*1). Neither genotype nor allele distribution of CYP2C19*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05). CONCLUSION: Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19*3 defective allele may contribute to reduced risk for the development of EH.
Adult ; Alleles ; Aryl Hydrocarbon Hydroxylases/*genetics ; Asian Continental Ancestry Group/genetics ; Female ; Genotype ; Homozygote ; Humans ; Hypertension/epidemiology/*genetics ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Young Adult

OBJECTIVETo evaluate the relationship between A46G and C79G polymorphisms in the β2-adrenergic receptor (ADRB2) gene and the incidence of essential hypertension (EH) among the Han Chinese population.

METHODSWe conducted a computer retrieval of PUBMED, EMBASE, CNKI, Wanfang and VIP databases prior to May 2010. Articles investigating the relationship of EH and ADRB2 gene polymorphism of Han group were found through literature search, including 15 articles on A46G and 10 articles on C79G. According to the including and excluding criteria, a Meta-analysis was conducted in EH and ADRB2 gene polymorphism of A46G and C79G. The association was examined by RevMan4.2 software through quantitative analysis.

RESULTSEight articles on A46G polymorphism (including 1078 EH cases and 788 control subjects) and six articles on C79G polymorphism (including 1367 EH cases and 1006 control subjects) were included in the current study. Meta-analysis showed that there was a significant association between A46G polymorphism and EH: genotype GG/(AA + AG) (fixed-effected model, OR = 1.35, 95%CI = 1.04 - 1.74, P = 0.02), genotype GG/AA (fixed-effected model, OR = 1.41, 95%CI = 1.06 - 1.89, P = 0.02). No significant association was found between C79G polymorphism and EH of Han group in China: G/C allele comparison (random-effected model, OR = 0.88, 95%CI = 0.55 - 1.39, P = 0.57).

CONCLUSIONSignificant association was found between A46G polymorphism of ADRB2 gene and EH, whereas no association could be found between C79G polymorphism and EH among Han Chinese population.

Alleles ; Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-2 ; genetics ; Risk Factors

OBJECTIVETo study the relationship between JWA polymorphisms and the susceptibility to hypertension in workers exposed to heat stress.

METHODSThe exposure group included 158 steelworkers and rollers and 76 workers unexposed to heat stress served as control group. The general information was collected according to a questionnaire and the blood pressure was examined for all subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to analyze the site 76 in promoter and site 723 in the 3rd exon of JWA gene in the peripheral lymphocytes. PHASE 2.0 software was utilized to calculate the haploid type.

RESULTSIn the exposure group, JWA76 G/G genotype frequencies of sub-group with normal blood pressure, sub-group with higher blood pressure and sub-group with hypertension were 82.35%, 69.70% and 65.00%, respectively, there were significant differences among 3 sub-groups (P < 0.05). JWA 76 G/G genotype frequencies decreased with blood pressure (χ² = 4.86, P = 0.027). The multiple logistic regression analysis showed that the subjects with G/C genotype were compared to the subjects with G/G genotype in the exposure group, the adjusted OR value was 3.67 (95%CI: 1.21 approximately 11.05) for the risk of hypertension and higher blood pressure. the subjects with GG/CT haploid type were compared to the subjects with non-GG/CT haploid type in the exposure group, the adjusted OR values for the risks of hypertension and higher blood pressure were 8.30 (1.39 approximately 49.44) and 8.55 (1.53 approximately 47.48), respectively.

CONCLUSIONThe gene polymorphisms at site 76 and GG/CT haploid type of JWA gene were associated with hypertension in workers exposed to high temperature.

Adult ; Blood Pressure ; genetics ; Control Groups ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Heat-Shock Proteins ; genetics ; Hot Temperature ; Humans ; Hypertension ; epidemiology ; genetics ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Polymorphism, Single Nucleotide ; Workplace