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Essential hypertension has a high rate of morbidity and mortality, primarily because of the associated complications. The Wellcome Trust Case Control Consortium recently conducted a genome-wide association study and identified six single nucleotide polymorphisms (SNPs) associated with essential hypertension. The Family Blood Pressure Program later...
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Context 1
... variables were significantly different between the Ansung and Ansan cohorts, as reported earlier by Kim et al. 11 The minor allele frequencies of the six SNPs in the KARE data were compared with the minor allele frequencies from the WTCCC data and dbSNP (The Single Nucleotide Polymorphism database) data. As shown in Table 2, the allele frequencies in the KARE data were similar to those in the HCB (Han Chinese in Beijing) and JPT (Japanese in Tokyo), but were different from those of the WTCCC and CEU (Caucasians in Europe). ...
Citations
... The heritability of hypertension is cited to range from 30% to 60% [62]. One of these genetic components is a polymorphism of the BCAT1 gene, which has been associated with increasing the risk of an individual developing hypertension in genome-wide studies [4,63,64]. The mechanism for this polymorphism is unknown, but it has been linked to increased salt sensitivity and is a marker of oxidative stress [65]. ...
The development of cardiovascular diseases (CVDs) is due to a complex interaction between the genome and the environment. Understanding how genetic differences in individuals contribute to their susceptibility to CVDs can help guide practitioners to give the best advice to achieve a favorable outcome for the patient. As genome technologies evolve, genotyping of individuals could be available to all patients using a simple saliva test. Large-scale genome-wide association studies and meta analyses have provided powerful insights into polymorphisms that may be predictive of disease and an individual's response to certain nutrients, but moving forward it is imperative that these insights can be applied in the medical setting to reduce the incidence and mortality of CVDs.
... P = 0.040). 33 Another study conducted in 101 Korean participants also found rs7961152 to be significantly associated with salt sensitivity after adjusting for potential confounders. 34 Our result was consistent with the above studies. ...
Background:
Salt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited.
Method:
A total of 342 essential hypertensives from Beijing were recruited in our study. A modified Sullivan's acute oral saline load and diuresis shrinkage test was conducted to each individual. Medical history and lifestyle risk factors were obtained by questionnaire. Generalized linear model was used to examine the associations of 29 single-nucleotide polymorphisms (SNPs) with SSBP and false discovery rate (FDR) was used to correct P values for multiple testing.
Results:
In the process of acute sodium loading, after adjusting for age and 24-hour urinary sodium concentration, SNPs in CYP11B2, PRKG1, SLC8A1 genes were significantly associated with systolic BP (SBP) rising in the additive and recessive model; SNPs in CYP4A11, PRKG1, SLC8A1, and ADRB2 genes were significantly associated with diastolic BP (DBP) rising. In the process of diuresis shrinkage, SNPs of CLCNKA, eNOS, PRKG1 gene were associated with SBP and DBP decreasing. After FDR correction, rs434082 in SLC8A1 gene was still significantly associated with blood pressure rising during salt load. In the additive model, A allele increased DBP of 2.8 mm Hg (FDR_q = 0.029) and MAP of 3.1 mm Hg (FDR_q = 0.029) after adjusting for age and 24-hour urinary sodium concentration.
Conclusion:
SLC8A1 gene may contribute to BP change in the process of acute sodium loading in a Han Chinese population.
... This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). the study of the pathogenesis of hypertension (Hong et al., 2009;Ehret et al., 2008;Maruthamuthu and Kandasamy, 2016;Yang et al., 2016;Zhu et al., 2011). FGF5 is one of the fibroblast growth factors and the existing studies showed that it played an important role in the control of the animal hair growth process (Higgins et al., 2014;Kubelkova and Macela, 2015;Haitham, 2016;Chen et al., 2013). ...
Objective
To explore the expression level of FGF5 in the peripheral blood of primary hypertension patients and its clinical significance.
Methods
The 34 patients with primary hypertension treated in this hospital from June 2012 to June 2014 were selected as the observation group, while the 25 patients at this hospital who had physical exam with heathy results were selected as control group. Venous blood was drawn early in the morning after an overnight fast. FGF5, mRNA and protein level changes in the peripheral blood cells and peripheral blood serum were analyzed by real-time fluorescence based quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). FGF5 gene SNP (rs16998073) were amplified by PCR and inserted into T vector, and its genetic variation were analyzed by sequencing. The relationship of FGF5 protein levels and genetic variation with diastolic/systolic blood pressure was also analyzed.
Results
Comparing with the control group, the observation group’s FGF5 mRNA and protein levels significantly increased in the peripheral blood cells and peripheral blood. The difference was statistically significant (P<0.05). Correlation analysis showed that FGF5 protein level and systolic/diastolic blood pressure were positively correlated (P <0.05). T/A genetic variation of FGF5 gene SNP (rs16998073) and diastolic/ systolic blood pressure were positively correlated (P <0.05).
Conclusion
The FGF5 mRNA and protein expression levels of the patients with primary hypertension were abnormal and had genetic variation, which were associated with blood pressure of the patients with primary hypertension.
... There have been several studies that examined the relationship between single nucleotide polymorphism (SNP) and blood pressure or hypertension via genome-wide association studies (GWAS) among Koreans [4][5][6][7][8][9][10][11][12]. However, the mechanism of blood pressure is not sufficiently explained by the genetic effect. ...
... Sample 2 was analyzed to clarify the association between urinary factors and blood pressure or hypertension, and to investigate interaction effects between urinary factors and tagging SNPs on the risk of hypertension. There have been several studies that examined the relationship between single nucleotide polymorphism (SNP) and blood pressure or hypertension via genome-wide association studies (GWAS) among Koreans [4][5][6][7][8][9][10][11][12]. However, the mechanism of blood pressure is not sufficiently explained by the genetic effect. ...
... Cont. Ratio, 24 h urinary Na-K ratio. 1 Adjusted for sex.2 Adjusted for age and sex. 3 Adjusted for age and sex.4 Mean ± standard deviation. ...
Hypertension is a complex disease explained with diverse factors including environmental factors and genetic factors. The objectives of this study were to determine the interaction effects between gene variants and 24 h estimated urinary sodium and potassium excretion and sodium-potassium excretion ratios on the risk of hypertension. A total of 8839 participants were included in the genome-wide association study (GWAS) to find genetic factors associated with hypertension. Tanaka and Kawasaki formulas were applied to estimate 24 h urinary sodium and potassium excretion. A total of 4414 participants were included in interaction analyses to identify the interaction effects of gene variants according to 24 h estimated urinary factors on the risk of hypertension. CSK rs1378942 and CSK-MIR4513 rs3784789 were significantly modified by urinary sodium-potassium excretion ratio. In addition, MKLN rs1643270 with urinary potassium excretion, LOC101929750 rs7554672 with urinary sodium and potassium excretion, and TENM4 rs10466739 with urinary sodium-potassium excretion ratio showed significant interaction effects. The present study results indicated that the mutant alleles of CSK rs1378942 and CSK-MIR4513 rs3784789 had the strongest protective effects against hypertension in the middle group of 24 h estimated urinary sodium-potassium excretion ratio. Further studies are needed to replicate these analyses in other populations.
... In spite of its seriousness, genetic factors that are related with hypertension are still remains elusive. Hypertension studies with genetic information have been reported using KARE (Korean Association REsource) cohorts, such as Genome-wide association study , nonsynonymous SNPs association study , replication association study (Hong et al., 2009& Jin et al., 2012, and candidate genes study . Blood pressure is determined by combination of cardiac output and resistances of peripheral blood vessels (Marc and Llorens-Cortes, 2011). ...
Development of hypertension is caused by complex contributions of genetic and environmental factors. In spite of the increased understanding of hypertension, genetic factors that contribute to hypertension largely remain elusive. ANO1 gene encoding a calcium-activated chloride channel has recently been reported to affect spontaneous hypertension in the animal model. In this report, we investigated possible association of the ANO1 gene with hypertension in human with ANO1 variants found in Korean population. Fourteen polymorphisms of ANO1 gene were analyzed to be associated with hypertension. Interestingly, the six polymorphisms that showed statistically significant association were all the male subjects. The highest significant SNP was rs7127129 (OR=1.14, CI: 1.02~1.28, additive P=0.023; OR=1.24, CI: 1.03~1.49, dominant P=0.025), and other five SNPs (rs2509153, rs11235473, rs10751200, rs10898827 and rs10899928) were also statistically associated with hypertension. Consequently, we found that the genetic variants of ANO1 present statistically significant associations with hypertension in human, especially, in male. To the best of our knowledge, this study is the first report describing association of genetic polymorphisms of ANO1 with hypertension in human.
... We apply the proposed multivariate GMDR method to the Korean Association Resource study on blood pressure: systolic blood pressure (SBP) and diastolic blood pressure (DBP). A number of authors have investigated the genome-wide association studies on blood pressure and hypertension for Korean population [24][25][26] and for others [27][28][29][30]. However, not much work has been done for gene-gene interaction analyses. ...
... We defined the hypertensive case as HP = 1 if SBP ≥ 140 mmHg or DBP ≥ 90 mmHg, and HP = 0, otherwise. Several genome-wide association studies (GWAS) have been performed on blood pressure by treating blood pressure as a quantitative trait [24][25][26][27][28][29]. In this study, we treated blood pressure as a binary trait HP representing whether the hypertension status is yes or no. ...
Recently, one of the greatest challenges in genome-wide association studies is to detect gene-gene and/or gene-environment interactions for common complex human diseases. Ritchie et al. (2001) proposed multifactor dimensionality reduction (MDR) method for interaction analysis. MDR is a combinatorial approach to reduce multi-locus genotypes into high-risk and low-risk groups. Although MDR has been widely used for case-control studies with binary phenotypes, several extensions have been proposed. One of these methods, a generalized MDR (GMDR) proposed by Lou et al. (2007), allows adjusting for covariates and applying to both dichotomous and continuous phenotypes. GMDR uses the residual score of a generalized linear model of phenotypes to assign either high-risk or low-risk group, while MDR uses the ratio of cases to controls.
In this study, we propose multivariate GMDR, an extension of GMDR for multivariate phenotypes. Jointly analysing correlated multivariate phenotypes may have more power to detect susceptible genes and gene-gene interactions. We construct generalized estimating equations (GEE) with multivariate phenotypes to extend generalized linear models. Using the score vectors from GEE we discriminate high-risk from low-risk groups. We applied the multivariate GMDR method to the blood pressure data of the 7,546 subjects from the Korean Association Resource study: systolic blood pressure (SBP) and diastolic blood pressure (DBP). We compare the results of multivariate GMDR for SBP and DBP to the results from separate univariate GMDR for SBP and DBP, respectively. We also applied the multivariate GMDR method to the repeatedly measured hypertension status from 5,466 subjects and compared its result with those of univariate GMDR at each time point.
Results from the univariate GMDR and multivariate GMDR in two-locus model with both blood pressures and hypertension phenotypes indicate best combinations of SNPs whose interaction has significant association with risk for high blood pressures or hypertension. Although the test balanced accuracy (BA) of multivariate analysis was not always greater than that of univariate analysis, the multivariate BAs were more stable with smaller standard deviations.
In this study, we have developed multivariate GMDR method using GEE approach. It is useful to use multivariate GMDR with correlated multiple phenotypes of interests.
... Genotyping. Candidate SNPs were selected from recent GWA studies and large candidate gene association studies [4,6,7,[13][14][15][16][17][18][19][20]. Whole blood specimens were collected from each individual into EDTA tubes, and genomic DNA was isolated from peripheral blood leukocytes using the Wizard Genomic DNA Purification Kit according to the manufacturer's instructions (Promega, Experimental Diabetes Research 3 Madison, WI, USA). ...
Hypertension and arterial stiffness are associated with an increasing risk of diabetes and cardiovascular diseases. This study aimed to identify genetic variants affecting hypertension and arterial stiffness in diabetic subjects and to compare genetic associations with hypertension between prediabetic and diabetic subjects. A total of 1,069 participants (326 prediabetic and 743 diabetic subjects) were assessed to determine the genetic variants affecting hypertension by analyzing 52 SNPs previously reported to be associated with hypertension. Moreover, the SNPs were tested for association with hemodynamic parameters related to hypertension. Out of the 52 SNPs analyzed, four SNPs including rs5326 (DRD1), rs1004467 (CYP17A1), rs2960306 (GRK4), and rs11191548 (near NT5C2) in diabetic subjects and rs1530440 (C10orf107) in prediabetic subjects showed a modest association with hypertension (P = 0.0265, 0.0020, 0.0066, 0.0078, and 0.0015, resp; all were insignificant after Bonferroni correction). Of these SNPs, rs1004467 in CYP17A1 was significantly associated with augmentation index in diabetic subjects who were not taking antihypertensive medication (P = 0.0001; corrected P = 0.006) but not in diabetic subjects receiving antihypertensive medication. This finding suggests that certain genetic variations found in diabetic subjects may confer arterial stiffness and the development of hypertension and also be affected by antihypertensive medication.
... A CNV study has reported population-dependent CNVs that inconsistently occur between ethnic groups (Redon et al., 2006). To date, a number of genomic variants associating SNP loci with susceptibility to common complex human diseases have been identified through genome-wide association studies (GWASs) (The WTCCC, 2007; Estivill and Armengol, 2007; Hong et al., 2009; Cho et al., 2009). Although some CNV studies have also reported associations with several complex disorders, the corresponding CNV data are scarce compared with SNP data. ...
... Although some CNV studies have also reported associations with several complex disorders, the corresponding CNV data are scarce compared with SNP data. Moreover, previous GWASs reported associations of SNPs with anthropometric traits including blood pressure (BP) and body mass index (BMI) in the Korean population (Hong et al., 2009; Cho et al., 2009), but no CNV association studies with these traits have been reported. The aims of our current study were as follows: 1) discover Korean CNV regions (CNVRs) in large-scale cohort samples; 2) examine additional loci that may be associated with hypertension-related traits; 3) compare association results of CNVs with those of previously known risk loci. ...
Hypertension is the major factor of most death and high blood pressure (BP) can lead to stroke, myocardial in-farction and cardiac failure. Moreover, hypertension is strongly correlated with body mass index (BMI). Al-though the exact causes of hypertension are still un-clear, some of genetic loci were discovered from ge-nome-wide association study (GWAS). Therefore, it is essential to study genetic variation for finding more ge-netic factor affecting hypertension. The purpose of our study is to conduct a CNV association study for hyper-tension-related traits, BP and BMI, in Korean individuals. We identified 2,206 CNV regions from 3,274 commun-ity-based Korean participants using the Affymetrix Ge-nome-Wide Human SNP Array 6.0 platform and per-formed a logistic regression analysis of CNVs with two hypertension-related traits, BP and BMI. Moreover, the 4,692 participants in an independent cohort were se-lected for respective replication analyses. GWAS of CNV identified two loci encompassing previously known hy-pertension-related genes: LPA (lipoprotein) on 6q26, and JAK2 (Janus kinase 2) on 9p24, with suggestive p-val-ues (0.0334 for LPA and 0.0305 for JAK2). These two positive findings, however, were not evaluated in the replication stage. Our result confirmed the conclusion of CNV study from the WTCCC suggesting weak associa-tion with common diseases. This is the first study of CNV association study with BP and BMI in Korean pop-ulation and it provides a state of CNV association study with common human diseases using SNP array.
... To date, there have been extensive GWAS results related to complex diseases such as Type II diabetes and hypertension. [19][20][21][22][23] However, there exist only a few GWAS results for PA. Only the effects of regular PA and sedentary behavior on risk factors for common diseases, health outcomes, and mortality rates have been emphasized. ...
Genome-wide association studies (GWAS) have successfully identified many genetic variants that are associated with many complex traits. For example, GWAS can be useful for understanding the genetic basis of physical activity (PA). To date, however, there have been only a few GWAS regarding PA. In this article, we overview some practical issues for more efficient GWAS for PA: phenotype definition of PA, the analysis method, population stratification, replication, and sample size. We discuss these issues within a large-scale GWA data set from the Korea Association REsource (KARE) project, including 8,842 samples and 352,228 single nucleotide polymorphism (SNP) markers. Information on PA was obtained from questionnaires, and GWA analysis was performed to find genetic associations between PA and SNP markers in the Korean population.
... We recapitulated the Wellcome Trust Case Control Consortium (WTCCC) GWAS on hypertension using KARE data, the same samples of which were used in this study (Hong, et al., 2009). The association analysis of the 6 SNPs that were published by the WTCCC hypertension study identified only 3 SNPs (rs6997709, rs7961152, and rs2820037) that were weakly associated (0.008<p<0.05) ...
Hypertension is a complex disease that is caused by the interaction of multiple genetic and environmental risk factors, affecting
30% adult in industrialized countries. The identification of genetic factors that impact one’s predisposition to hypertension
and its progression is an ongoing challenge. A genome-wide association study of African-Americans, who have one of the highest
rates of hypertension in the world, was reported. We replicated the GWAS results in 8842 unrelated Koreans. Fifteen of the
30 reported SNPs were analyzed for their association with blood pressure and hypertension. Linear regression was used to analyze
blood pressure as a quantitative trait in 7551 subjects, and a case-control study was performed using 1968 hypertensive cases
and 4452 normotensive controls by logistic regression analysis. The quantitative trait study demonstrated a moderate association
of 2 SNPs, rs9301196 (p=4.9×10−3 for diastolic blood pressure) and rs2823756 (p=0.04 for systolic blood pressure), which were also associated with hypertension (p=0.042 and p=6.3×10−3, respectively). Further, 3 SNPs were associated with hypertension (p=0.042 for rs7902529, p=0.027 for rs10135446, and p=0.01 for rs4613079) but not with blood pressure. Based on the moderate association signals and the low proportion of positive
signals, this cross validation between African-Americans and Asians suggests that association studies of blood pressure traits
require a larger number of subjects and a more refined design.
KeywordsBlood pressure–Hypertension–Genome-wide association study–Replication
