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Blood pressure (BP) is characterized by spontaneous oscillation over time, which is described as BP variability (BPV). The current study aimed to investigate whether short-term BPV was correlated with hypertensive nephropathy in Han Chinese individuals with hypertension. A single-center prospective cohort study of 300 Han Chinese participants with hypertension was conducted in Taiwan. Five different BPV parameters were derived from ambulatory BP monitoring (ABPM), including standard deviation (SD), weighted SD (wSD), coefficient of variation (CoV), successive variation (SV), and average real variability (ARV). Renal event was defined as > 50% reduction in baseline estimated glomerular filtration rate (eGFR). The average age of the participants was 63.5 years. The baseline eGFR was 84.5 mL/min/1.73 m 2 . The participants were divided into two groups according to the wSD of systolic BP (SBP). Survival was assessed via a Kaplan-Meier analysis. During the 4.2-year follow-up, the participants with the highest SBP wSD tertile had a greater number of renal events (6.0%) than their counterparts (0.5%) (log-rank test, p = .007). The Cox proportional hazard regression model was used to assess the independent effects of BPV, and results showed that 24-h SBP (HR = 1.105; 95% CI = 1.020-1.197, p = .015) and 24-h DBP (HR = 1.162; 95% CI = 1.004-1.344, p = .044) were independently associated with renal events. However, BPV parameters were only associated with renal events univariately, but not after adjusting for baseline characteristics, 24-h mean BP, and office BP. Therefore, the risk of hypertensive nephropathy was independently associated with 24-h mean BP, but not with ambulatory BPV, in Han Chinese participants with hypertension., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non-diabetic hypertensive patients aged 20-50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24-h ambulatory BP monitoring, and 24-h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24-h ambulatory BP, and 24-h urine catecholamine excretion. In men, 24-h urine total catecholamine levels were correlated with 24-h SBP (r = 0.103, p = .008) and 24-h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24-h urine total catecholamine levels and 24-h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01-3.29, p = .048) and 24-h urine total catecholamine (β = 5.03, 95% CI 0.62-9.44, p = .025) were both independently associated with 24-h SBP; being male was independently associated with 24-h DBP (β = 3.55, 95% CI 2.26-4.85, p < .001). In conclusion, Chinese men with hypertension had higher SNS activity than women, and SNS activity was independently associated with 24-h ambulatory BP in men rather than in women. These findings suggest that different hypertensive treatment strategies should be considered according to patient sex., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Recent studies have suggested that circadian genes have important roles in maintaining the circadian rhythm of the cardiovascular system. However, the associations between diurnal BP changes and circadian genes remain undetermined. We conducted a genetic association study of young-onset hypertension, in which 24-h ambulatory blood pressure (BP) monitoring was performed. A total of 23 tag single-nucleotide polymorphisms (SNPs) on 11 genes involved in circadian rhythms were genotyped for correlations with diurnal BP variation phenotypes. A permutation test was used to correct for multiple testing. Five tag SNPs within five loci, including rs3888170 in NPAS2, rs6431590 in PER2, rs1410225 in RORββ, rs3816358 in BMAL1 and rs10519096 in RORα, were significantly associated with the non-dipper phenotype in 372 young hypertensive patients. A genetic risk score was generated by counting the risk alleles and effects for each individual. Genotyping was performed in an additional independent set of 619 young-onset hypertensive subjects. Altogether, non-dippers had a higher weighted genetic risk score than dippers (1.67±0.56 vs. 1.54±0.55, P<0.001), and the additive genetic risk score also indicated a graded association with decreased diurnal BP changes (P=0.006), as well as a non-dipper phenotype (P=0.031). After multivariable logistic analysis, only the circadian genetic risk score (odds ratio (OR), 1550; 95% confidence interval (CI), 1.225-1.961, P<0.001) and the use of β-blockers (OR, 1.519; 95% CI, 1.164-1.982, P=0.003) were independently associated with the presence of non-dippers among subjects with young-onset hypertension. Genetic variants in circadian genes were associated with the diurnal phenotype of hypertension, suggesting a genetic association with diurnal BP changes in essential hypertension.

Background: Resistant hypertension (RH) is a common clinical condition associated with increased cardiovascular mortality and morbidity in older patients. Several factors and conditions interfering with blood pressure (BP) control, such as excess sodium intake, obesity, diabetes, older age, kidney disease, and certain identifiable causes of hypertension are common in patients resistant to antihypertensive treatment. Arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV), is increasingly recognized as an important prognostic index and potential therapeutic target in hypertensive patients. The aim of this study was to determine whether there is an association between RH and arterial stiffness., Methods: This study included 1,620 patients aged ≥ 65 years who were referred or self-referred to the outpatient hypertension unit located at a single cardiovascular center. They were separated into normotensive, controlled BP, and resistant hypertension groups. Home BP, blood laboratory parameters, echocardiographic studies and baPWV all were measured., Results: The likelihood of diabetes mellitus was significantly greater in the RH group than in the group with controlled BP (odds ratio 2.114, 95% confidence interval [CI] 1.194-3.744, P=0.010). Systolic BP was correlated in the RH group significantly more than in the group with controlled BP (odds ratio 1.032, 95% CI 1.012-1.053, P=0.001). baPWV (odds ratio 1.084, 95% CI 1.016-1.156, P=0.015) was significantly correlated with the presence of RH. The other factors were negatively correlated with the existence of RH., Conclusion: In patients aged ≥ 65 years, the patients with RH have elevated vascular stiffness more than the well controlled hypertension group. baPWV increased with arterial stiffness and was correlated with BP levels. Strict BP control is necessary to prevent severe functional and structural vascular changes in the course of hypertensive disease.

Thiazide diuretics are associated with an increased risk of hypokalemia. However, pharmacogenetic markers of thiazide-induced changes in serum potassium are not well studied. The aim of this study was to investigate possible predictors of serum potassium changes after thiazide treatment. Nondiabetic hypertensive patients with a systolic blood pressure of ⩾140 or a diastolic blood pressure of ⩾90 mm Hg were enrolled in our study. After 2 weeks of lifestyle modification and diet instruction, patients with persistently elevated blood pressure were given 50 mg of hydrochlorothiazide every morning for 2 weeks. Twenty single-nucleotide polymorphism (SNP) markers were selected from two candidate genes, SLC12A3 and WNK1. Serum potassium levels were checked before and after hydrochlorothiazide treatment. A total of 75 patients eventually qualified for enrollment in our study. They received 50 mg of hydrochlorothiazide every morning for 2 weeks. Six SNPs in WNK1 (rs11064524, rs4980973, rs12581940, rs880054, rs953361, and rs10849582) were correlated with decreases in serum potassium. None of the SLC12A3 polymorphisms were correlated with decreases in serum potassium. After Bonferroni's correction, only rs4980973 was correlated with decreases in serum potassium (corrected P=0.014). Multivariate stepwise linear regression analysis revealed that the changes in serum potassium levels were independently associated with the baseline potassium level (β=-0.587, 95% confidence interval=-0.875--0.299, P=0.0001) and WNK1 rs4980973 (A/A and A/G vs. G/G, β=-0.418, 95% confidence interval=-0.598--0.237, P=0.00002). In conclusion, the baseline potassium level and the WNK1 rs4980973 polymorphism were independent predictors of decreases in serum potassium after short-term hydrochlorothiazide treatment in nondiabetic hypertensive patients.

Background: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined., Method and Results: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p<0.05,). The T risk allele resulted in a cumulative increase in nighttime PP (β = 1.036 mm Hg, se. = 0.298, p<0.001 per T allele). An independent community-based cohort containing 3325 Taiwanese individuals (mean age, 50.2 years) was studied to investigate the genetic impact of rs897876 polymorphisms in determining future cardiovascular events. After an average 7.79 ± 0.28 years of follow-up, the TT genotype of rs897876 was independently associated with an increased risk (in a recessive model) of coronary artery disease (HR, 2.20; 95% CI, 1.20-4.03; p = 0.01) and total cardiovascular events (HR, 1.99; 95% CI, 1.29-3.06; p = 0.002), suggesting that the TT genotype of rs897876C, which is associated with nighttime pulse pressure in young-onset hypertension patients, could be a genetic prognostic factor of cardiovascular events in the general cohort., Conclusion: The TT genotype of rs897876C at 2p14 identified in young-onset hypertensive had higher nighttime PP and could be a genetic prognostic factor of cardiovascular events in the general cohort in Taiwan.

Background: High-sensitivity C-reactive protein (hs-CRP) is a sensitive inflammatory marker suggested for cardiovascular risk stratification. This study aimed to assess the potential genetic determinants for serum hs-CRP levels in a cohort with well-controlled nondiabetic hypertension., Materials and Methods: Ethnic Chinese nondiabetic hypertensive patients were enrolled in Taiwan. They received comprehensive evaluation including history taking, physical check-up, blood pressure (BP) measurement, 24-h ambulatory BP monitoring and blood sampling. Serum hs-CRP levels were determined. CRP genotyping was performed in two stages. In the first stage, 4 single-nucleotide polymorphisms (SNPs) of CRP including rs1572970, rs2794520, rs3093077 and rs2808630 were investigated in the 400 participants. In the second stage, only SNPs significant in the first stage were selected for complete genotyping in the whole population., Results: Total 915 consecutive patients (40·9 ± 7·3 years, 68·3% male) completed the study. Two of the 4 SNPs including rs1572970 and rs3093077 were correlated to hs-CRP levels in the whole population. Stepwise multiple linear regression indicated that age (P = 0·001), body mass index (P < 0·001), waist-hip ratio (P = 0·032), smoking habits (P = 0·001), night-time systolic BP (P = 0·040), total cholesterol (P = 0·005) and CRP rs3093077 polymorphism (P < 0·001) were independently associated with serum hs-CRP levels. Overall, genetic correlates explained 2·4%, BMI explained 11·9% and all other clinical correlates explained 4·8% of interindividual variability in serum hs-CRP level., Conclusion: C-reactive protein genotype contributed limitedly to serum hs-CRP levels in subjects with well-controlled hypertension, suggesting the impacts of clinical rather than genetic determinants to serum hs-CRP levels for cardiovascular risk stratification in this intermediate-risk Taiwanese cohort., (© 2013 The Authors. European Journal of Clinical Investigation © 2013 Stichting European Society for Clinical Investigation Journal Foundation.)

Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10(-16) to <10(-33)). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3'UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects.

Background: Although emerging evidence shows angiotensin-receptor blockers (ARBs) may have a beneficial effect against Alzheimer's disease (AD), the association is not consistent. We investigated the association between ARB use and the risk of development of AD using a nationwide, population-based cohort database in Taiwan., Methods and Results: In total, 16,426 newly diagnosed hypertensive patients who were administered ARB without a previous diagnosis of AD were identified from the Taiwan National Health Insurance database. The comparison group consisted of hypertensive patients who did not receive ARB, and were matched to exposed individuals using propensity score by enrolled time, age, sex, and comorbidities. During an average of 5.24 ± 2.01 years of follow-up, a total of 1,031 cases (3.13%) of new AD occurred. The log-rank test showed no significant difference in the AD occurrence rate between subjects exposed to ARBs and non-exposed controls [488 (2.97%) vs. 543 (3.29%), P=0.221]. After adjusting for age, sex, comorbidities, and medications, only advanced age [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.12-1.13, P<0.001), female sex (HR 1.18, 95% CI 1.04-1.33, P=0.011), diabetes (HR 1.53, 95% CI 1.31-1.79, P<0.001), but not ARB (HR 1.08, 95% CI 0.96-1.22, P=0.222) were independently associated with AD development., Conclusions: The use of ARB was not significantly associated with a reduction of risk of AD in Asian patients with essential hypertension.

Introduction: Arterial stiffness may contribute to left ventricular hypertrophy (LVH). This study was conducted to evaluate the independent factor of LVH and the quantification of LVH by electrocardiogram (ECG) to predict the degree of aortic stiffness using brachial-ankle pulse wave velocity (baPWV) in subjects with hypertension., Materials and Methods: A total of 984 consecutive patients who were diagnosed as having essential hypertension were entered into the study. baPWV determination, ECG and blood sampling were performed after a 12-hour overnight fast. LVH was diagnosed using electrocardiography; Romhilt-Estes point score was subsequently calculated. Participants were separated into LVH and non-LVH groups. Additional factors associated with LVH were examined using multivariate analyses., Results: The non-LVH groups were younger (P = 0.001), had less men (P = 0.001), lower systolic and diastolic blood pressure and pulse pressure (P < 0.001 for each) and lower baPWV (P < 0.001). Stepwise multiple logistic regression analysis demonstrated that sex, age, systolic blood pressure and baPWV are independent factors. Using a baPWV value of 1825 cm/sec, the area under the receiver operating characteristic curve was 0.644 and the highest discriminating sensitivity and specificity were 60% and 65%, respectively., Conclusion: Aortic stiffness may be related to electrocardiographically determined LVH in patients with hypertension. Thus, stiffening of large arteries, together with increased systolic blood pressure, seems to significantly contribute to the pathogenesis of LVH. Quantification of LVH by ECG can also predict the degree of aortic stiffness.

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations.

Objective: The plasma adiponectin level, a potential upstream and internal facet of metabolic and cardiovascular diseases, has a reasonably high heritability. Whether other novel genes influence the variation in adiponectin level and the roles of these genetic variants on subsequent clinical outcomes has not been thoroughly investigated. Therefore, we aimed not only to identify genetic variants modulating plasma adiponectin levels but also to investigate whether these variants are associated with adiponectin-related metabolic traits and cardiovascular diseases., Research Design and Methods: We conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) associated with high molecular weight forms of adiponectin levels by genotyping 382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 SNP chips. The culpable single nucleotide polymorphism (SNP) variants responsible for lowered adiponectin were then confirmed in another 559 YOH subjects, and the association of these SNP variants with the risk of metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and ischemic stroke was examined in an independent community-based prospective cohort, the CardioVascular Disease risk FACtors Two-township Study (CVDFACTS, n = 3,350)., Results: The SNP (rs4783244) most significantly associated with adiponectin levels was located in intron 1 of the T-cadherin (CDH13) gene in the first stage (P = 7.57 × 10(-9)). We replicated and confirmed the association between rs4783244 and plasma adiponectin levels in an additional 559 YOH subjects (P = 5.70 × 10(-17)). This SNP was further associated with the risk of MS (odds ratio [OR] = 1.42, P = 0.027), T2DM in men (OR = 3.25, P = 0.026), and ischemic stroke (OR = 2.13, P = 0.002) in the CVDFACTS., Conclusions: These findings indicated the role of T-cadherin in modulating adiponectin levels and the involvement of CDH13 or adiponectin in the development of cardiometabolic diseases.

Background: While genetic variants of renin-angiotensin-aldosterone system (RAAS) may modify the blood pressure (BP) response to thiazide diuretics, there was no evidence of genetic variations in renin (REN) playing a role. This study aimed to address the potential effects of genetic variations of RAAS on the response to initial treatment of hydrochlorothiazide (HCTZ)., Materials and Methods: We enrolled nondiabetic hypertensive patients with a systolic blood pressure (SBP) ≥140 or a diastolic blood pressure (DBP) ≥90mmHg, who were either previously untreated or unsatisfactorily treated. After lifestyle modification and diet instruction for 2weeks, 90 patients with persistently elevated BP were given HCTZ 50 mg every morning for 2 weeks. Single nucleotide polymorphism markers were selected from genes involving in RAAS, including rs7079 and rs699 of angiotensinogen, rs4293 and rs4353 of angiotensin-converting enzyme and rs1464816 and rs11240688 of REN., Results: The patients were divided into three groups according to the SBP response after HCTZ. The upper 1/3 responders had older age (P=0·035), higher SBP (P=0·039), higher pulse pressure (P=0·006) and lower plasma REN activity (PRA) (P=0·020) when compared with the lower 1/3 responders. Renin rs11240688 CC polymorphism (β=9·931, corrected P=0·012), Log PRA (β=7·451, P=0·004) and baseline SBP (β=0·299, P=0·006) were the independent predictors for the BP lowering response., Conclusions: In addition to PRA, renin rs11240688 CC polymorphism may also independently predict the effect of HCTZ., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Cardiovascular risk increases with the presence of both metabolic syndrome (MetS) and hypertension (HTN). Although the adiponectin (ADIPOQ) gene has been reported to be involved in MetS, its association with HTN remained undetermined. This study aimed to investigate the association of ADIPOQ gene with the phenotypes of HTN and MetS., Methods: A total of 962 participants from 302 families from the Taiwan young-onset hypertension genetic study were enrolled. Plasma adiponectin were measured, and association analysis was conducted by using GEE regression-based method. Another study, of 1448 unrelated participants, was conducted to replicate the association between ADIPOQ gene and variable phenotypes of MetS with or without HTN., Results: Among 962 subjects from family samples, the lowest plasma adiponectin value was observed in MetS with HTN component (9.3±0.47 µg/ml) compared with hypertensives (13.4±0.74 µg /ml) or MetS without HTN (11.9±0.60 µg/ml, P<0.05). The SNP rs1501299 (G276T) in ADIPOQ gene was found associated with the presence of HTN in MetS (odds ratio for GG+GT vs. TT = 2.46; 95% CI: 1.14-5.3, p = 0.02), but not rs2241766 (T45G). No association of ADIPOQ gene with HTN alone or MetS without HTN was observed. The significant association of the SNP rs1501299 (G276T) with the phenotype of presence of HTN in MetS was confirmed (odds ratio for GG+GT vs. TT = 2.15; 95% CI: 1.1-4.3) in the replication study., Conclusions: ADIPOQ genetic variants were selectively and specifically associated with the concomitant presence of MetS and HTN, suggesting potential genetic linkage between MetS and HTN.

Introduction: The association between the arterial stiffness and the severity of left ventricular (LV) diastolic function in hypertension has not been fully evaluated. This study was conducted to evaluate the relationship of aortic stiffness by brachial-ankle pulse wave velocity (baPWV) to parameters reflecting the atherosclerosis and the severity of LV diastolic function in patients with hypertension., Methods: LV ejection fraction, the ratio of peak velocity of early rapid filling and peak velocity of atrial filling (E/A ratio) and LV mass index were determined with echocardiography in 800 patients with hypertension. LV diastolic function was estimated by pulsed-tissue Doppler imaging (TDI) echocardiography, averaging diastolic mitral annular velocity measurements (Emav, Amav and Emav/Amav ratio) from 2 separate sites (basal septal and lateral). The baPWV was measured by the volume rendering method., Results: Stepwise multiple logistic regression analysis demonstrated that the independent factors of LV diastolic function were deceleration time, baPWV, age and Emav/Amav ratio. The receiver- operator characteristic curve demonstrated a baPWV of 1566 cm/sec was useful to discriminate mild LV diastolic dysfunction (sensitivity, 78%; specificity, 78%), and that a baPWV of 1730 cm/sec was useful to discriminate moderate LV diastolic dysfunction (sensitivity, 73%; specificity, 57%)., Conclusions: Increased baPWV relates not only to the parameters reflecting atherosclerosis but also to those reflecting LV diastolic dysfunction. TDI-detected LV diastolic dysfunction is accompanied by increased aortic stiffness in essential hypertension. Therefore, quantification of aortic stiffness can predict the degree of LV diastolic function.

Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG., (Copyright 2008 Wiley-Liss, Inc.)

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

Objectives: Angiotensin converting enzyme (ACE) plays major roles in the pathogenesis of cardiovascular diseases (CVD). However, findings on the relations between ACE variants and CVD have not been consistent. The purpose of this study was to map quantitative trait loci (QTL) for serum ACE activity, a heritable endophenotype of cardiovascular diseases (estimated heritability = 0.58)., Methods: With 1,271 individuals from 373 young-onset (age

We report the case of a 65-year-old man with a 6-year history of hypertension who presented with dilated cardiomyopathy, a transient cerebrovascular event, paroxysmal sweating, and intractable hypertension. Coronary angiography revealed no abnormality, but diagnostic testing was pursued because of the severe sweating and hypertension. Two-dimensional echocardiography showed 4-chamber dilatation with decreased left ventricular contractility. Further investigation, including a computed tomographic scan of the abdomen, led to a diagnosis of pheochromocytoma. Surgical resection of a left adrenal pheochromocytoma quickly resolved the patient's hypertension and resulted in substantially improved cardiac function after 4 months. Although pheochromocytoma has rarely been reported in the presence of both dilated cardiomyopathy and cerebrovascular events, it should be included in the differential diagnosis when patients present with dilated cardiomyopathy and a cerebrovascular event that have no obvious cause.