醛固酮合酶基因多态性与老年原发性高血压的关系

目的探讨醛固酮合酶(CYP11B2)基因-344C/T多态性与老年原发性高血压(EH)的相关性。方法以人群为基础进行老年人EH病例-对照研究,应用PCR-RELP技术对289例武汉地区汉族老年人的CYP11B2基因-344C/T多态性进行分析。结果武汉地区汉族老年人群CYP11B2基因-344C/T多态性以TT和CT为主要基因型,C等位基因较少见。CYP11B2基因-344C/T多态性与老年人EH有相关性(P0.05)。结论武汉地区汉族老年人群CYP11B2基因-344C/T多态性与EH存在相关性,老年高血压人群携带CC+CT基因型频率较高。     

武汉地区汉族人群醛固酮合酶基因多态性与原发性高血压的关系

目的 :探讨武汉地区汉族人群醛固酮合酶 (CYP11B2 )基因 344C/T多态性频率分布特点及其与原发性高血压 (EH)的关系。方法 :以人群为基础进行EH病例 对照研究 ,应用PCR RELP技术对 2 11例武汉地区汉族人的CYP11B2基因 344C/T多态性进行分析。结果 :武汉地区汉族人群CYP11B2基因 344C/T多态性以TT和CT为主要基因型 ,C等位基因较少见 ,其频率为 2 4 % ,明显低于文献报道的欧洲白种人 (P <0 .0 1) ,亦低于日本人 (P <0 .0 5 )。CYP11B2基因 344C/T多态性与EH无明显相关性 (P >0 .0 5 )。结论 :武汉地区汉族人群CYP11B2基因 344C/T多态性频率分布有着与欧洲白种人以及日本人不同的特点 ,且它与EH没有明显的相关性     

原发性高血压患者醛固酮合酶基因-344C/T多态性与血浆醛固酮浓度的关系

目的探讨汉族原发性高血压人群醛固酮合酶(CYP11B2)基因-344C/T多态性频率分布特点及其与血浆醛固酮浓度的关系。方法应用PCR-RELP技术对103例原发性高血压患者的CYP11B2基因-344C/T多态性进行分析。结果汉族原发性高血压人群CYP11B2基因-344C/T多态性以TT和CT为主要基因型,C等位基因较少见。与携带TT基因型的高血压患者比较,CT CC基因型携带者的血浆醛固酮浓度明显增高(148．52±55．63 ng/ml vs 122．85±38．22 ng/ml,P=0．015)。结论汉族原发性高血压人群CYP11B2基因-344C/T多态性与血浆醛固酮浓度有关。     

醛固酮合酶基因多态性与原发性高血压关系的研究

目的 :探讨醛固酮合酶CYP11B2基因 -344C/T多态性与原发性高血压的相关性。方法 :运用多聚酶链反应—限制性片段长度多态性分析 (PCR RFLP)了解醛固酮合酶CYP11B2基因 -344C/T基因型在原发性高血压患者 (n =10 8,原发性高血压组 )和正常血压患者 (n =14 6 ,对照组 )的分布情况。结果 :等位基因C、T在原发性高血压组和对照组的分布频率分别为 0 2 8,0 72和 0 36 ,0 6 4,基因频率分布符合Hardy Weinberg平衡 ,样本具有群体代表性 ,两组人群的基因型和等位基因频率无明显差异 (P >0 0 5 )。结论 :在中国人群中 ,醛固酮合酶CYP11B2基因 -344C/T多态性与原发性高血压无显著性相关     

醛固酮合酶基因多态性与高血压患者血压及RAAS激素水平的相关性研究

目的探讨醛固酮合酶(CYP11B2)基因-344C/T多态性与高血压患者血压及肾素-血管紧张素-醛固酮系统(RAAS)激素水平的相关性。方法用放射免疫法检测171例原发性高血压患者(92例男性,79女性)RAAS激素水平,包括血浆肾素活性(PRA)、血浆血管紧张素II(AT-II)和醛固酮(ALD)水平。用聚合酶链反应(PCR)和限制性酶切方法检测所有患者的CYP11B2基因-344C/T多态性,按CC、CT和TT三种基因型分组。分析其与高血压患者血压及RAAS激素水平的相关性。结果 CYP11B2基因-344C/T多态性与高血压患者血压及血浆PRA和AT-II水平无关,但与血浆ALD水平相关,TT和CT基因型者的血浆ALD水平要高于CC基因型者,其差异有统计学意义(0.66±0.36or0.61±0.35versus0.42±0.23nmol/L,P=0.036)。结论本研究显示,高血压患者的CYP11B2基因-344C/T多态性与血浆ALD水平相关,提示该多态性可能参与了高血压患者血浆ALD水平的调节。     

醛固酮合酶基因-344C/T多态性与老年心房颤动的关系

目的探讨醛固酮合酶(CYP11B2)基因-344C/T多态性与老年心房颤动(AF)的关系。方法选择老年心血管系统疾病的患者和健康体检者238例,根据既往病史及心电图将入选者分为2组,心电图诊断AF患者为AF组115例,心电图正常的窦性心律患者为窦律组123例,应用PCR-RELP技术检测CYP11B2基因-344C/T多态性,并进行分析。结果 CYP11B2基因-344C/T多态性以TT和CT为主要基因型,与窦律组比较,AF组患者CT+CC基因型更多见(χ~2=4.66,P<0.05)。结论武汉地区汉族老年人群中,AF人群携带CC+CT基因型频率较高,CYP11B2基因-344C/T多态性可能与AF相关。     

醛固酮合酶CYP11B2(-344C/T)基因多态性与2型糖尿病肾病的相关性

目的探讨醛固酮合酶CYP11B2(-344C/T)基因多态性与2型糖尿病肾病的关系。方法采用聚合酶链反应-限制性酶切片段长度多态性分析(PCR-RFLP)技术检测95例2型糖尿病患者(其中合并肾病患者32例,未发生肾病63例)和175例健康对照组醛固酮合酶CYP11B2(-344C/T)基因多态性。结果糖尿病肾病组、糖尿病非肾病组和健康对照组两两比较,CYP11B2基因型和等位基因分布均无统计学差异(P>0.05)。与健康对照组比较,糖尿病肾病组和糖尿病非肾病组的血浆醛固酮水平均有极明显增高(P<0.01);糖尿病肾病患者CYP11B2(-344C/T)基因多态性的3种基因型间血浆醛固酮水平比较差异有显著性(P<0.05)。结论醛固酮合酶CYP11B2(-344C/T)基因多态性与2型糖尿病肾病的发生无显著相关性,但可能与血浆醛固酮水平有关。     

醛固酮合成酶基因CYP11B2(-344T/C)多态性对北京汉族人群高血压患者缬沙坦降压疗效的影响

目的探讨醛固酮合成酶基因CYP11B2(-344T/C)多态性与北京汉族人原发性高血压的关系及对缬沙坦降压疗效的影响。方法采用多聚酶链式反应结合限制性内切酶片段长度多态性分析方法检测1999年8月至2003年10月首都医科大学宣武医院345例原发性高血压(EH)患者和156名健康人(NE)醛固酮合成酶基因CYP11B2(-344T/C)多态性。并测定各组人群的诊室血压、24h血压以及各项生化指标。其中98例高血压患者给予缬沙坦80mg,每日1次,用药4周,测定用药前后的血压指标。结果EH组CC CT基因型频率显著高于NE组;EH组C等位基因频率显著高于NE组(P<0.01)。CC CT基因型用药后的收缩压下降值、舒张压下降值、平均动脉压下降值及24h收缩压下降值、24h舒张压下降值、24h平均动脉压下降值均显著大于TT基因型(P<0.05)。结论醛固酮合成酶基因CYP11B2(-344T/C)多态性与北京汉族人原发性高血压明显相关,并且可能是缬沙坦降压疗效的有效预测因子。     

肾素-血管紧张素-醛固酮系统基因多态性与大动脉粥样硬化性卒中的相关性:中国南方汉族人群研究

目的 研究肾素-血管紧张素-醛固酮系统血管紧张素原(angiotensinogen,AGT)基因M235T、血管紧张素Ⅱ1型受体(angiot ensinⅡtype 1 receptor,AGTR1)基因A1166C、醛固酮合酶( aldosterone synthase,CYP11B2)基因- 344C/T多态性与中国南方汉族人群大动脉粥样硬化性卒中(large-artery atherosclerosis,LAA)的相关性.方法 采用聚合酶链反应和基因测序技术对中国南方汉族LAA患者和正常对照者AGT基因M235T、ATGR1基因A1166C和CYP11B2基因- 344C/T多态性进行基因分型,并通过二分类logistic回归分析确定这3种基因多态性与LAA的相关性.结果 共纳入LAA患者107例和142名健康对照者.LAA组AGT基因235TT基因型(66.36％对50.70％,x2=6.122,P=0.047)和T等位基因(79.44％对70.07％,x2=5.581,P=0.018)频率显著高于对照组,AGTR1基因1166CC基因型(0％对0％,x2=1.494,P=0.222)和C等位基因(7.48％对4.93％,x2=1.399,P=0.237)频率与对照组无显著性差异,CYP11B2基因- 344CC基因型(9.35％对4.23％,x2=3.603,P=0.165)和C等位基因(27.10％对26.06％,x2=0.069,P=0.793)频率与对照组亦无显著性差异.二分类logistic回归分析显示,这3种基因多态性与单纯性LAA患病均无显著相关性.合并高血压的LAA患者AGT基因235TT基因型(68.00％对41.90％,x2=12.446,P=0.002)和T等位基因(79.33％对64.76％,x2=8.993,P=0.003)频率均显著高于血压正常对照组,logistic回归分析显示,暴露于TT基因型的优势比(odds ratio,OR)为2.153[ 95％可信区间(confidence interval,CI)0.789 ～5.872],T等位基因的OR值为2.089(95％ CI1.285 ～3.396).结论 AGT基因M235T多态性与南方汉族人群单纯性LAA无关,但可能与合并高血压的LAA患病风险相关;CYP11B2基因- 344C/T多态性和AGTR1基因A1166C多态性与南方汉族人群LAA发病无关.     

醛固酮合成酶基因多态性（C／T）与高血压患者左室肥厚相关性研究

目的　研究原发性高血压患者醛固酮合成酶CYP11B2 (- 344C/T)多态性与左室肥厚的关系。方法　应用多聚酶链式反应 (PCR)、限制性内切酶方法检测 4 2 0例原发性高血压患者CYP11B2 (- 344C/T)基因型。用M型超声心动图测量舒张末期左心室内径 (LVDd) ,左心室后壁厚度 (LVPWT) ,舒张末期室间隔厚度 (INSTd)。结果　三组基因型间醛固酮 (ALD)浓度差异无显著性 ;左室肥厚 (LVH)与非左室肥厚 (NLVH)组基因型、等位基因频率分布差异无显著性 (P >0 0 5 )。LVH组血浆ALD浓度显著高于NLVH组 (15 6 .95± 4 7.5 5vs 14 6 .33± 4 5 2 9,P <0 0 5 ) ;按ALD水平四分位数分成四级 ,OR值随醛固酮水平的增加而递增 ,呈现明显的剂量反应关系。结论　醛固酮合成酶CYP11B2 (- 344C/T)多态性与左室肥厚无关 ;ALD水平是高血压患者左室肥厚的危险因素。     

Association of the human CYP11B2 gene and essential hypertension in southwest Han Chinese population: a haplotype-based case-control study

Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure (BP). The aldosterone-synthase gene (CYP11B2) has been regarded as a candidate gene for essential hypertension. To address this issue, we carried out a haplotype-based, case-control study to explore the association between a human CYP11B2 gene and essential hypertension (EH) in the southwest Han population of China (n = 1020 individuals). Four tag single-nucleotide polymorphisms (SNPs) (rs4536, rs4545, rs3097, and rs3802230) and the C-344T polymorphism, as well as the K173R polymorphism in the CYP11B2 gene, were genotyped using the PCR-RFLP method. Single-locus analysis showed that the C allele of rs3802230 was significantly more prevalent in the EH subjects as compared to control subjects, adjusted for covariates. Haplotype analysis showed that the haplotype AAGC constructed by the tag SNPs (rs4536, rs4545, rs3097, and rs3802230), which carried the susceptible rs3802230 C allele, significantly increased the risk of essential hypertension with an odds ratios equal to 3.56 (P = 0.0001). The present results indicated that the rs3802230 C allele might be a risk marker for essential hypertension and haplotype AAGC might confer high genetic susceptibility to essential hypertension in a southwest Han Chinese population.     

广东汉族原发性高血压患者CYP2C9和ACE基因多态性的分布特征

目的:观察沙坦类药物代谢酶细胞色素氧化酶P450 2C9(CYP2C9)基因的多态性和血管紧张素Ⅰ转换酶(angiotension I-coverting enzyme,ACE)基因的多态性在广东汉族原发性高血压(essential hypertension,EH)患者中的分布特征。方法:应用PCR、基因测序及琼脂糖凝胶电泳等方法,对206例EH患者CYP2C9和ACE基因型进行检测分析。结果:广东汉族EH患者中CYP2C9基因的1075位C等位基因的频率为3.2%,广东汉族EH患者中CYP2C9*3等位基因的频率与广东人群相比,无显著性差异;ACE基因D、I等位基因的频率分别为56.3%和43.7%。ACE基因的D等位基因频率显著高于广东及国内其他地区正常人群中的频率(P0.05)。结论:在广东汉族EH患者中,未发现CYP2C9*3等位基因与EH有关,而ACE基因的D等位基因可能和EH有关,同时,对EH患者进行CYP2C9和ACE基因的基因型的检测,可能对临床个体化降压治疗具有一定的指导意义。     

醛固酮合成酶基因多态性与高血压及左室肥厚的关系

目的：本研究旨在观察血管紧张素转换酶（ACE）基因I／D多态性和醛固酮合成酶（CYP11B2）基因－344C／T多态性与高血压（EH）及左室肥厚（LVH）的相关性。方法：将136例原发性高血压病患者分为LVH组72例,无LVH组64例;应用多聚酶链式反应（PCR）、限制性内切酶方法检测ACE和CYP11B2基因的多态性。结果：（1）无LVH组LVH组ACE基因I／D多态性基因型和等位基因分布差异均有显著性（P＜0．05）,LVH组Ⅱ基因型和Ⅰ等位基因频率显著高于无LVH组。（2）无LVH组与LVH组CYP11B2基因－344C／T多态性基因型和等位基因分布差异均有显著性（P＜0．05）,LVH组CT基因型和C等位基因频率显著高无LVH组。（3）LVH组中的CT＋Ⅱ联合基因型频率高于无LVH组（P＜0．05）。结论：（1）ACE型I／D和CYP11B2基因－344C／T多态性与高血压发生无相关性。（2）ACE基因Ⅱ多态性与LVH相关。(3）CYP11B2基因－344CT基因型与LVH相关。（4）CYP11B2基因－344CT基因型和ACE基因Ⅱ基因型共存对LVH的发病具有协同作用。     

新疆汉族和哈萨克族人群内皮型一氧化氮合酶基因T786C和G894T多态性与原发性高血压的相关分析

目的探讨新疆汉族和哈萨克族内皮型一氧化氮合酶基因G894T、T786C多态性与原发性高血压的相关性。方法选取新疆塔城地区哈萨克族高血压患者363人和正常血压者370人,选取汉族高血压患者346人,正常血压者385人,运用多重单碱基延伸分型技术进行内皮型一氧化氮合酶基因G894T、T786C多态性分析,阐明两民族基因型、等位基因频率分布、连锁不平衡模式及构建的单体型与原发性高血压的相关性。结果超重、肥胖、甘油三酯异常及年龄51岁以上是两民族患高血压的共同相关危险因素。总人群、原发性高血压组及正常血压组中两民族内皮型一氧化氮合酶基因G894T、T786C位点等位基因频率分布差异均有统计学意义(P<0.05),两位点间不存在强连锁不平衡。汉族和哈萨克族人群内皮型一氧化氮合酶基因两位点共构成4种单体型:GT(75.3%和79.6%)、GC(10.8%和10.5%)、TT(5.7%和9.8%)及TC(8.2%和0.1%)。两民族单体型频率分布最高为GT,汉族和哈萨克族人群单体型频率分布最低分别是TC、TT,且两民族间单体型GT、TT、TC频率分布差异有统计学意义(P<0.05)。结论新疆汉族和哈萨克族人群内皮型一氧化氮合酶基因G894T、T786C位点多态可能与原发性高血压不相关。     

CYP11B2 gene polymorphism and essential hypertension among Tibetan,Dongxiang and Han populations from northwest of China

Essential hypertension (EH) is a complex multifactorial condition influenced by both genetic and environmental factors; aldosterone synthase (CYP11B2) is a key enzyme which involves in the terminal steps of aldosterone synthesis. The result of relationship between C-344T of CYP11B2 polymorphism and EH was controversial. This study was undertaken to investigate the association of C-344T polymorphism with EH in the populations of Tibetan, Dongxiang and Han from northwest of China. A total of 2115 participants aged 18–70 years were enrolled in this study. In total, 1776 blood samples, including 545 Tibetan (305 hypertensive and 240 normotensive), 530 Dongxiang (254 hypertensive and 276 normotensive) and 701 Han (338 hypertensive and 363 normotensive), were analyzed successfully by using Snapshot minisequencing method, 30 samples were also performed by direct sequencing (5 hypertensive and 5 normotensive in each population, respectively). The frequencies of genotype and allele of CYP11B2 (C-344T) were not significantly different between EH group and control group in every ethnic population (p > 0.05). However, in female population of Tibetan, the frequencies of CC and CT genotype and C allele in EH group were higher than in control (p < 0.05) group. The frequencies of CC genotype and C allele in both the normotensive controls and EH patients in Tibetan population were higher than in Dongxiang and Han populations. Our study suggests that there is lack of association between C-344T polymorphism of CYP11B2 gene and EH in Dongxiang and Han populations, whereas the polymorphism was correlated with EH in female population of Tibetan.     

三个候选基因多态性与高血压病关联的研究

目的 探讨转化生长因子β1（TGF-β1）T869C、醛固酮合成酶（CYP1182）-344T／C和Oα-内收蛋白Gly460Trp3个单核苷酸多态性（SNPs）与原发性高血压（EH）的关系。方法采用限制性片段长度多态性和突变基因分离PCR法,在396例EH患者和214例正常人中分析T869C、-344T／C和Gly460Trp多态性的基因型分布。结果在单基因研究中,女性EH患者与对照组比较,TGF-β1T869C基因型和等位基因频率差异有统计学意义（P值分别=0．017,0．014）;与T等位基因携带者相比,CC纯合子EH患病率差异有统计学意义（OR=2．97,95％CI 1．38～6．32,P=0．004）;而男性则两组间T869C基因型分布和等位基因频率差异无统计学意义（P〉0．05）。采用多基因联合分析,TGF-β1 CC纯合子中,CYP1182Tr纯合子EH患病率高于C等位基因携带者（OR=1．99,95％CI 1．01～3．74,P=0．03）。结论TGF-β1 T869C多态性可能与中国汉族女性EH相关;在EH人群中,TGF-β1 T869C和CYP1182-344T／C多态性可能有协同作用。     

Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population

ABSTRACT

Background and Objectives: Essential hypertension is a complex progressive cardiovascular disorder. Renin–angiotensin aldosterone system (RAAS) plays a major role in blood pressure regulation. Aldosterone, synthesized in the adrenal cortex by aldosterone synthase is encoded by the CYP11B2 gene. This case-control study was aiming to investigate the relationship between the aldosterone synthase gene (CYP11B2) biallelic polymorphism in the promoter at position ?344 (?344C/T) with essential hypertension and left ventricular hypertrophy in the Egyptian population.

Methods: This study was conducted on 100 hypertensive patients (group I) and 50 healthy control subjects (group II). Serum aldosterone, plasma renin, ARR levels were investigated. Echocardiography was done to evaluate LV dimensions. Genotyping of the CYP11B2 gene was performed by PCR/RFLP confirmed by direct sequencing.

Results: Our study revealed that CYP11B2 (?344T) allele was significantly higher than (?344C) allele in hypertensive patients as compared to healthy control (OR-2.51; 95% CI:1.3–3.5; P = 0.002) and ?344TT genotype was associated with increased LVMI as compared with ?344CC genotype (P = 0.001).

Conclusion: A Significant association was observed between the CYP11B2 (?344C/T) polymorphism and ?344T allele and essential hypertension in the Egyptian population. Also, we found that the CYP11B2 ?344C/T polymorphism and ?344T allele are associated with left ventricular hypertrophy which may predispose to cardiovascular complications of hypertension.     

Modulation of aldosterone levels by −344 C/T CYP11B2 polymorphism and spironolactone use in resistant hypertension

Interindividual variability in plasma aldosterone levels comprises environmental and genetic sources. Increased aldosterone levels have been associated with higher risk of hypertension and target-organ damage related to hypertension. Aldosterone excess and intravascular volume expansion are implicated in pathophysiology of resistant hypertension (RH). We sought to investigate whether −344 C/T polymorphism (rs1799998) in aldosterone synthase gene (CYP11B2) is associated with plasma aldosterone levels in patients with resistant hypertension. Sixty-two patients with resistant hypertension were enrolled in this cross-sectional study. Genotypes were obtained by allelic discrimination assay using real time polymerase chain reaction. Multivariable linear regression was used to identify whether TT genotype was a predictor of aldosterone levels. No differences in clinical and laboratorial parameters were found among genotype groups. We found an additive effect of the T allele on plasma aldosterone concentration in RH. Also, there was higher aldosterone levels in TT homozygous under use of spironolactone compared with C carriers and compared with TT subjects who was not under use of spironolactone. TT genotype and the use of spironolactone were significant predictors of aldosterone levels in RH subjects. Plasma aldosterone concentration is significantly associated with −344 C/T CYP11B2 polymorphism and with the treatment with spironolactone in resistant hypertensive subjects.