Essential Hypertension In Chinese Research Articles

Interaction between mitochondrial NADH dehydrogenase subunit-2 5178 C > A and clinical risk factors on the susceptibility of essential hypertension in Chinese population

BackgroundThe mitochondrial genotype 5178 cytosine/adenine (5178 C > A) within the NADH dehydrogenase subunit-2 gene (ND2) was proved to associate with longevity and predispose resistance to adult-onset diseases. This study aimed to confirm the interactive effects between ND 25178 C > A and clinical risk factors on the susceptibility of essential hypertension in Chinese general population.Materials and MethodsThe relationship between the ND2 5178 C > A variation and the risk of hypertension was investigated in 817 hypertensives and 821 matched normotensives. The interactive effects between ND2 5178 C > A and clinical risk factors were evaluated.ResultsThe ND2 5178 A allele was more frequent in normotensives than in hypertensives (32.64% vs. 24.24%; adjusted OR: 0.62, 95% CI: 0.49–0.79, P = 1.3 × 10− 4). After stratification, the significant association between ND2 5178 C > A and hypertension was found only in current smokers (OR: 0.44, 95% CI: 0.31–0.62), but not in non-current smokers (p < 0.01 for interaction). Smoking status (OR: 1.51, 95% CI: 1.11–2.06) and high triglycerides (OR: 1.57, 95% CI: 1.10–2.24) were found independently associated with hypertension only in carriers of 5178 C allele but not in carriers of 5178 A allele.ConclusionsIn conclusion, ND2 5178 A allele could confer a lower risk for essential hypertension in Chinese by the interaction with smoking status. The higher risk of hypertension imposed by smoking and high TG may be altered by ND2 5178 A allele.

Influence of PRKCH gene polymorphism on antihypertensive response to amlodipine and telmisartan

ABSTRACTThis study aimed to evaluate the effect of PRKCH rs2230500 genetic polymorphism on efficacy of amlodipine and telmisartan for patients with hypertension. A total of 136 essential hypertension (EH) patients were treated with amlodipine (70 patients) or telmisartan (66 patients), respectively. Genetic polymorphism was genotyped by Sanger sequencing. Both baseline and post-treatment blood pressure (BP) and heart rate were measured to evaluate the influence of genetic polymorphism on the antihypertensive response. No significant difference in the absolute decrease in diastolic blood pressure (DBP),systolic blood pressure (SBP), and mean arterial pressure (MAP) was observed among PRKCH rs2230500 genotypes after 4-week amlodipine or telmisartan therapy (p > 0.05). However, when compared with carriers or GG genotype, the antihypertensive effect of PRKCH rs2230500 GA/AA carriers was superior in telmisartan treatment group. PRKCH rs2230500 gene polymorphism is significantly related to the efficiency in telmisartan therapy (p = 0.02). The PRKCH rs2230500 may influence the antihypertensive efficacy of telmisartan in Chinese EH patients, and further studies are needed to confirm these findings.

Leptin is associated with heart rate recovery in Chinese hypertensive patients

ABSTRACTElevated serum leptin concentrations are closely related to sympathetic nervous system activation in essential hypertension (EH); however, it is not clear whether or not they are associated with parasympathetic nervous system impairment in EH. Heart rate recovery (HRR) is a reproducible method used to assess parasympathetic activity. This study aimed to investigate the relationship between serum leptin and HRR in Chinese untreated EH patients. This was a cross-sectional study enrolling 471 Chinese EH patients (205 men, 266 women; mean age 63.1 years). HRR was calculated during an incremental cardiopulmonary exercise test. Simple and multiple regression analyses were used to assess the correlation between serum leptin level and HRR value. Serum leptin levels elevated with increasing BP values. Moreover, univariate analysis revealed that the HRR value was negatively correlated with serum leptin (r = −0.037, P < 0.01). In multiple regression analysis, the age-adjusted serum leptin level was negatively correlated with HRR (β = −0.268, P < 0.01). Serum leptin remained negatively associated with HRR (β = −0.017, P < 0.01) after further adjustments for factors including age, systolic blood pressure, total cholesterol, and several factors that correlated with HRR. Our findings demonstrated that a raised serum leptin concentration is related to HRR blunt, which suggests that the role of leptin in the development of EH might be associated with impairment of the parasympathetic nervous system as well.

Positive association between KCNJ5 rs2604204 (A/C) polymorphism and plasma aldosterone levels, but also plasma renin and angiotensin I and II levels, in newly diagnosed hypertensive Chinese: a case-control study.

Variants in G protein-coupled inward rectifier K+ channels 4 (GIRK4 also known as KCNJ5) gene are associated with primary aldosteronism, which is the most common cause of secondary hypertension. The KCNJ5 rs2604204 variant was shown to be common (minor allele frequency=32.5%) in Chinese patients with essential hypertension (EH). The relationship between KCNJ5 variant and plasma aldosterone (ALD) levels in EH patients has not been reported. We collected 229 patients with newly diagnosed EH without any antihypertensive agents. According to the median standing plasma ALD, high-ALD and control groups were divided. Clinical data and blood samples were collected. KCNJ5 rs2604204 genotype was determined by PCR. The results showed that the levels of triglyceride, uric acid, insulin, insulin resistance (IR) index, renin, angiotensin I (Ang I), angiotensin II (Ang II), cortisol, 24 h mean systolic blood pressure (SBP) and daytime mean SBP were significantly increased in the high-ALD group than those in the control group, as well as 24 h s.d. of SBP and diastolic BP (DBP), and 24 h coefficient of variance of SBP and DBP. Notably, the distribution frequency of AC and CC genotypes, and the C allele of KCNJ5 were also significantly higher in the high-ALD group. Logistic regression analysis showed that the C allele of KCNJ5 rs2604204 was one risk factor for increased plasma ALD in Chinese EH patients (P=0.008, odds ratio=2.2 (95% confidence interval 1.2-4.1)). Our findings indicated that the variation of plasma ALD might be associated with increased IR and BP variability. Moreover, KCNJ5 rs2604204 polymorphism was related to increased plasma ALD level, but also plasma renin, Ang I and II levels in newly diagnosed, never-treated EH patients.

Influence of G-protein β-Polypeptide 3 C825T Polymorphism on Antihypertensive Response to Telmisartan and Amlodipine in Chinese Patients.

Background:G-protein β-polypeptide 3 (GNB3) is a β subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs.Methods:A total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism.Results:Baseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group.Conclusion:The GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.

Relationship between Electroencephalogram and Perceived Stress in Essential Hypertension Patients

To explore the relationship between electroencephalogram and perceived stress in Chinese essential hypertension (EH) patients. Totally 60 EH patients were enrolled as the case group,and 60 gender-and age-matched healthy subjects as the control group. Graded mental arithmetic was used as a psychological stressor. The physiological values of electroencephalogram (Theta,Alpha,sensorimotor rhythm,and Beta) were recorded at baseline and in mission period and recovery period. Subjects were instructed to complete the Perceived Stress Scale. The electroencephalogram Theta value was significantly different between the case group and the control group (t=4.01,P=0.048). In the case group,the fluctuating Theta value was correlated with the control dimension in the Perceived Stress Scale (r=-0.26,P=0.044). Also in the case group,with the score of "sense of control" as the dependent variable and the fluctuating value of Theta after stress as the independent variables,regression analysis was performed. The opt-in standard was≤0.05 and the culling standard was≥0.01. The Results shows that the fluctuating value of Theta after stress in the case group met the requirements to enter the equation and could explain 5.2% of "sense of control" dimension. The Theta values associated with the sleeping and creativity decrease under stressful situations in EH patients following the increaed sense of pressure due to failure in controlling the pressure events.

Genetic variants of the class A scavenger receptor gene are associated with essential hypertension in Chinese.

The class A scavenger receptor, which is encoded by the macrophage scavenger receptor 1 (MSR1) gene, is a pattern recognition receptor (PPR) primarily expressed in macrophages. It has been reported that genetic polymorphisms of MSR1 are significantly associated with many cardiovascular events. However, whether it links genetically to essential hypertension (EH) in Chinese is not defined. We performed an independent case-control study in a Chinese population consisting of 617 EH cases and 620 controls by genotyping three single nucleotide polymorphisms (SNPs) of MSR1. We found that rs13306541 and rs3747531 were significantly associated with an increased risk of EH with per allele odds ratio (OR) of 1.63 [95% confidence interval (CI): 1.27-2.09; P<0.001] and 1.29 (95% CI: 1.09-1.52; P=0.003), respectively. Individuals with 2-4 risk alleles had a 2.03-fold (95% CI: 1.48-2.78) increased risk of EH compared with those having none of the risk alleles (P for trend <0.001). Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of EH in combination with traditional risk factors of EH in Chinese population.

Relationship between eNOS 894G&amp;gt;T Polymorphism and the Antihypertensive Efficiency of Two Dihydropyridine Calcium Channel Blocker Drugs, Azelnidipine and Nitrendipine, in Chinese EH Patients

Background: Dihydropyridine calcium-channel blockers (dCCBs) were widely used in anithypertensive treatment. The aim of this study was to examine the effect of polymorphisms of CACNA1C, eNOS and RGS2 on the antihypertensive efficiency of dihydropyridine calcium channel blocks (dCCBs) in Chinese patients with essential hypertension (EH). Methods: A total of 107 untreated Chinese mild to moderate EH patients were enrolled in this study, and had been prescribed azelnidipine or nitrendipine as monotherapy. All patients who had gave informed consent for genetic research were divided into two groups: treated with azelnidipine or nitrendipine for at leaset 6 weeks. Five polymorphisms of three blood pressure (BP) and hypertension susceptible genes were studied in our research, and these polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Every patients’ BP and heart rate were measured at 0 week, 2 weeks, 4 weeks and 6 weeks. The biochemical parameters of blood were detected before and 6 weeks after the administration. Adverse effects were evaluated at the last visitation. Results: Both the systolic and diastolic BP levels were significanlty decreased after six weeks of dCCBs treatment, from 149.3 ± 9.2 mmHg to 132.2 ± 11.7 mmHg and form 97.9 ± 3.0 mmHg to 85.5 ± 7.5 mmHg, as well as the levels of TP, TBIL, CHO and LDL, the P-values were P=0.017, P=0.045, P=0.039, P=0.041 respectivley. As 11 of 75 patients appeared adverse reactions, the rate of adverse effects showed no difference in various genotypes. There were significant interactions between eNOS G894T polymorphism and △DBP, △MBP on azelnidipine therapy patients, but not in nitrendipine, the GG genotype carriers were more sensitive in blood decrease than GT/TT genotype carriers (P<0.05). Conclusion: CCBs had potential hepatoprotective and antiatheroscloresis effects for Chinese EH paitents. And the eNOS G894T polymorphism is associated with the hypotensive effect of azelnidipine.

Racial difference in aldose reductase C-106T genetic polymorphism and association with essential hypertension.

To investigate the distribution of aldose reductase (AR) C-106T genetic polymorphism in Chinese Han population and its association with the risk for essential hypertension (EH). The AR C-106T polymorphism was genotyped in 148 Chinese EH patients and 137 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution between groups was contrasted by Χ(2)- test and the degree of genetic association was evaluated by 95% confidence interval (CI). Frequency of the variant AR C-106T allele was 13.9% (95% CI: 11.2%-16.6%) in the controls, which was significantly lower than that in the Japanese (18.4% in 712 individuals, P=0.0063), the Australians (37.9% in 240 individuals, P<0.0001) and the Brazilians (34.7% in 62 individuals, P<0.0001). The frequency of AR C-106T allele was 11.7% (95% CI: 7.9%-15.5%) in the EH patients. No significant difference in the allele frequency was observed between the EH patients and the controls (P=0.147). There is obvious racial difference in the distribution of AR C-106T polymorphism. The polymorphism is not associated with the risk for EH.

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients.

Albuminuria is an independent predictor of renal and cardiovascular complications in hypertensive subjects. We previously showed that lectin-like oxidized low density lipoprotein receptor 1 (OLR-1) polymorphisms at G501C are associated with susceptibility to essential hypertension and serum C-reactive protein levels. We have now investigated a possible association between OLR-1 polymorphisms at G501C, genotyped by PCR-RFLP, and severity of albuminuria in 307 hypertensive Chinese subjects and 225 age- and sex-matched controls. Urine albumin concentration /urine creatinine concentrations (ACR) were measured to evaluate the severity of albuminuria. Hypertensive subjects had a significantly higher frequency of the CC genotype and the C allele of the OLR-1 polymorphism than controls; this was also true for . hypertensive subjects with macroalbuinuria and microalbuminuria compared to those with normoalbuminuria. The mean ACR levels and mean serum C-reactive protein levels in CC carriers were significantly higher than in GG and GC carriers. There was a significant, positive correlation between serum hs-C-reactive protein levels and ACR levels. We conclude that OLR-1 polymorphisms at G501C affect the severity of albuminuria in essential hypertension patients.

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients

G501C polymorphism of the oxidized LDL receptor gene is associated with albuminuria in Chinese essential hypertension patients

A Systemic Review of the Relationship Between Aldosterone Synthase – 344 C/T Polymorphism and Hypertension in Han

Many studies reported the association between aldosterone synthase gene CYP11B2 polymorphism and essential hypertension in Chinese. So far, no meta- analysis was conducted between the etiology of essential hypertension and CYP11B2 -344 C/T polymorphism in Han Chinese, the majority (93% of the total population) in China. Recruited literature was based on searching the Cochrane Library, MEDLINE, EMBASE, the Chinese Biomedicine Database (CBM), CNKI, VIP, and reference lists of articles without language restrictions. Nine studies with case-control involving 4259 unselected essential hypertension patients and 3213 controls were included in the analysis. From the nine homogeneous studies with gender, age, and ethnicity matched controls, we found no significant association between the etiology of essential hypertension and the -344 C/T variant in Han Chinese with random effect models (for homozygous CC: odds ratio (OR), 1.04, 95% confidence interval (CI), 0.791.37, P = 0.79; for allele C: OR, 1.04, 95% CI, 0.921.18, P = 0.56). No significant association was observed between CYP11B2 -344 C/T polymorphism and hypertension susceptibility in both sexes. Current large sample analysis did not support the association between the etiology of essential hypertension and CYP11B2 - 344 C/T polymorphism in Han Chinese.

Angiotensin II type 1 receptor gene A1166C polymorphism and essential hypertension in Chinese: a meta-analysis

We performed a meta-analysis with the aim of assessing the association of the angiotensin II type 1 (AT(1)) receptor gene A1166C polymorphism with essential hypertension in Chinese case-control studies. Studies were searched from the Chinese Biomedicine Database, the China National Knowledge Infrastructure platform, Pubmed and Medline, using the search terms 'hypertension', 'angiotensin II type 1 receptor', 'AT(1)R', 'polymorphism', 'China' and 'Chinese', without limiting to any specific language. The strength of the association between the A1166C polymorphism and hypertension was evaluated by the odds ratio (OR) with the corresponding 95% confidence interval (CI). The analyses were performed with Cochrane RevMan software version 4.2. Overall, the variant genotype AC/CC was associated with a statistically increased essential hypertension risk with the pooled OR 1.48 (95% CI: 1.20-1.83). In the subgroup analyses, the association was also significant among studies using Northern populations, Southern populations, Han Chinese and hospital-based controls. The age did not influence the relationship between the AT( 1) receptor A1166C polymorphism and hypertension in the subgroup analyses. The present meta-analysis suggests that the AT(1) receptor 1166 AC/CC genotype is associated with susceptibility to hypertension in the Chinese population.

Genetic variants in mitochondrial tRNA genes are associated with essential hypertension in a Chinese Han population

Background Of multiple factors contributing to essential hypertension, mitochondrial variants exhibited the trends for serving as molecular and genetic markers for the disease in last five years. However, previous studies focused on African-American or Caucasian pedigrees, knowledge of mitochondrial tRNA genes and population-based Chinese hypertensives were limited. Methods We performed sequence analysis in tRNA genes, hot spots for cardiovascular diseases, in 270 Chinese Han essential hypertensives and 270 controls. Lymphoblastoid cell lines were immortalized by transformation with the Epstein–Barr virus. Rates of oxygen consumption in intact cells were determined with a YSI 5300 oxygraph (Yellow Springs Instruments) on samples, harboring variants in tRNA genes. Results There were 26 variants in tRNA genes that were found in hypertensives and these variants were not in controls. Functional analysis found that these variants may lead to deficiencies in tRNA 3′ end metabolism and/or impairment of critical subunits of the respiratory chain. Most importantly, the oxygen consumption rate in cells harboring variants T4454C ( P = 0.0010) and A4263G ( P = 0.0001) decreased as compared to the average level of control cell lines. Conclusions Variants located in mitochondrial tRNA genes may have biologic plausibility to implicate in the pathogenesis of Chinese essential hypertension.

Association between Aldosterone Synthase CYP11B2 Polymorphism and Essential Hypertension in Chinese: A Meta-Analysis

A thymidine-to-cytosine substitution in the –344 promoter region of the aldosterone synthase gene (CYP11B2) has been associated with essential hypertension in some but not all studies conducted in Chinese. We performed a meta-analysis to evaluate the association of the –344C/T polymorphism with essential hypertension in Chinese. A total of 7,472 individuals (4,259 unselected hypertensive patients and 3,213 normotensive controls) from 9 case-control studies were included in the present investigation. Significant associations between the risk of hypertension and the CC genotype and C allele frequencies were found in a total of 19 studies. Our findings support the notion that the CYP11B2 –344C/T polymorphism is associated with essential hypertension. In addition, C allele frequency was found to be lower in southern Chinese controls than in their northern counterparts, and the higher TT genotype homozygous frequency in the southern Chinese supports the hypothesis that the northern Chinese are of southern origin.

Polymorphisms of the β1-adrenergic receptor gene are associated with essential hypertension in Chinese

The beta1-adrenergic receptor (ADRB1) plays a pivotal role in mediating signal transduction of the sympathetic-adrenal system, which is involved in the regulation of cardiac output and peripheral resistance. Our goal was to determine whether the polymorphisms Arg389Gly (rs1801253) and Ser49Gly (rs1801252) of the ADRB1 gene were associated with essential hypertension in Chinese. We tested our hypothesis in two independent case-control studies, one comprised 481 patients with hypertension and 529 control subjects, and the other study comprised 212 patients and 325 control subjects. All subjects were genotyped for Arg389Gly and Ser49Gly polymorphisms. The first study showed that the Arg389Arg genotype of the ADRB1 gene was associated with risk of hypertension [odds ratio (OR) 1.77, 95% confidence interval (CI) 1.09-2.98; p=0.008], and the association was replicated in the second independent population (OR 1.65, 95% CI 1.07-2.89, p=0.01). The patients with the Arg389Arg genotype had significantly higher diastolic blood pressure (DBP) than did those with Arg389Gly genotype as well as those with Gly389Gly genotype (100.29+/-11.01 mm Hg vs. 95.33+/-13.10 mm Hg and vs. 96.17+/-12.18 mm Hg, respectively, p=0.01, p=0.02). The association was replicated in the second study (103.7+/-13.3 mm Hg vs. 97.31+/-12.9 mm Hg and vs. 96.29+/-13.4 mm Hg, respectively, p=0.03, p=0.02). Heart rate also showed an association (in first study: 79.43+/-9.90 bpm vs. 74.87+/-8.96 bpm, vs. 73.92+/-8.18 bpm, respectively, p=0.02, p=0.014; in the second study: 81.12+/-8.99 bpm vs. 74.85+/-7.97 bpm and vs. 73.89+/-9.12 bpm, p=0.007, p=0.006, respectively). No association was seen between systolic blood pressure (SBP) and any of the three genotypes at amino acid position 389 in hypertensive patients, neither between the Ser49Gly polymorphisms and hypertension, nor between the Ser49Gly genotypes and DBP and heart rate. The polymorphisms of the ADRB1 gene were associated with essential hypertension. The Arg389Gly polymorphism of the ADRB1 gene confers higher risk for hypertension.

Human microRNA-155 on Chromosome 21 Differentially Interacts with Its Polymorphic Target in the AGTR1 3′ Untranslated Region: A Mechanism for Functional Single-Nucleotide Polymorphisms Related to Phenotypes

Animal microRNAs (miRNAs) regulate gene expression through base pairing to their targets within the 3' untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. We mapped annotated SNPs onto a collection of experimentally supported human miRNA targets. Of the 143 experimentally supported human target sites, 9 contain 12 SNPs. We further experimentally investigated one of these target sites for hsa-miR-155, within the 3' UTR of the human AGTR1 gene that contains SNP rs5186. Using reporter silencing assays, we show that hsa-miR-155 down-regulates the expression of only the 1166A, and not the 1166C, allele of rs5186. Remarkably, the 1166C allele has been associated with hypertension in many studies. Thus, the 1166C allele may be functionally associated with hypertension by abrogating regulation by hsa-miR-155, thereby elevating AGTR1 levels. Since hsa-miR-155 is on chromosome 21, we hypothesize that the observed lower blood pressure in trisomy 21 is partially caused by the overexpression of hsa-miR-155 leading to allele-specific underexpression of AGTR1. Indeed, we have shown in fibroblasts from monozygotic twins discordant for trisomy 21 that levels of AGTR1 protein are lower in trisomy 21.

Association of alpha-adducin gene and G-protein beta3-subunit gene with essential hypertension in Chinese

To investigate the relationship between the alpha-adducin (ADD1) gene G460W and the G-protein beta 3-subunit (GNB3) gene C825T polymorphisms and essential hypertension (EH) in a northern Chinese Han population. Peripheral blood samples were collected from 256 hypertensive patients and 495 normotensive controls. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphisms of ADD1 and GNB3 genes. Their body mass index, blood lipids, blood glucose and blood uric acid levels were also determined. The allele frequencies of the ADD1 gene G460W and the GNB3 gene C825T polymorphisms were in Hardy-Weinberg equilibrium. The WW frequency in the EH group was 35.2%, significantly higher than that in the normal group (27.4%, chi(2) = 4.768, P = 0.029, OR = 1.43). Adjusted for the conventional risk factors of hypertension, alpha-adducin polymorphism still played an independent role on systolic blood pressure. The genotypes CC, CT, and TT of the GNB3 gene in the EH group were 20%, 52%, and 28% respectively, not significantly different from those in the control group (21%, 53%, and 26% respectively, P = 0.755). The frequencies of the alleles C and T of the GNB3 gene C825T were 46% and 54% respectively, not significantly different from those of the normotensive controls (47% and 53% respectively, P = 0.561). Body mass index, blood lipids, and glucose level did not differ significantly among the three genotype groups in both EH and normotensive control groups. The alpha-adducin gene may be a susceptible gene to EH in northern Chinese Han population, however, the GNB3 gene C825T polymorphism may not play a significant role in EH in the same population.

β2 Adrenergic Receptor Gene Arg16Gly Polymorphism is Associated with Therapeutic Efficacy of Benazepril on Essential Hypertension in Chinese

Background: There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by β2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. Methods and Results: We conducted a family‐based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15‐day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family‐based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15‐day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. Conclusion: Our family‐based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.

Alpha-adducin gene polymorphism is associated with essential hypertension in Chinese: a case-control and family-based study.

A polymorphism at position 460(G <-- W) of the alpha-adducin gene was found to be associated with essential hypertension in some but not all studies. The aim of the present study was to further investigate the association of the alpha-adducin 460W allele with essential hypertension in Chinese population. Individuals from a population-based sample (n = 748) and 95 nuclear families and 47 discordant sibships were studied by questionnaire as well as by physical examination and biochemical analyses. The alpha-adducin gene G460W polymorphism was determined by polymerase chain reaction and restriction enzyme digestion. Chi-square test, one-way analysis of variance, logistic regression, linear regression, haplotype-based haplotype relative risk and transmission/disequilibrium test analyses were used to determine the association between the alpha-adducin G460W polymorphism and essential hypertension. In the case-control study, the prevalence of hypertension was higher in individuals with the WW genotype (40.0%) as compared with those with the GW and GG genotype (31.7%) (chi2 = 4.768, P = 0.029, odds ratio = 1.43). Adjusted for the conventional risk factors of hypertension, alpha-adducin polymorphism still plays an independent role on systolic blood pressure. We confirmed the results of our case-control study by observing a significant preferential transmission of the 460W allele of the alpha-adducin to the affected subjects in another northern Chinese population (for haplotype-based haplotype relative risk, chi2 = 6.24, P = 0.01; and for the transmission/disequilibrium test, chi2 = 4.69, P = 0.03). The present findings show a positive association between the alpha-adducin G460W polymorphism and essential hypertension in a northern Chinese population. This evidence indicates that the alpha-adducin gene may be a susceptible gene to essential hypertension.