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。     

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。     

CYP11B2及APOA5基因多态性与原发性高血压的相关性研究

目的:探讨湖南地区原发性高血压患者醛固酮合成酶基因CYP11B2-344C/T及载脂蛋白A5APOA5-1131C/T基因多态性频率分布情况,并分析CYP11B2-344C/T及APOA5-1131C/T多态性与原发性高血压发病风险的关系。方法:185例原发性高血压患者为原发性高血压组,另选取180例正常体检者为对照组,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)测定两组CYP11B2及APOA5基因多态性。结果:原发性高血压组CC、CT基因型显著高于对照组,C等位基因频率高于对照组(P0.05)。结论:CYP11B2基因及APOA5基因在原发性高血压患者中呈多态性分布,两者可能为原发性高血压的候选基因。     

新疆哈萨克族隔离群醛因合成酶基因CYP11B2T(-344)C多态性与高血压的关联性研究

目的探讨哈萨克族人群醛固酮合成酶基因CYP11B2T(-344)C多态性与原发性高血压关联性.方法应用聚合酶链反应、限制性内切酶方法检测了新疆巴里坤县186例哈萨克族原发性高血压患者和168例正常人群CYP11B2基因T(-344)C多态性.结果哈萨克族正常人群及高血压患者的CYP11B2基因T(-344)C多态CC、Ct、TT基因型频率分别为0.12,0.61 0.27,和0.20,0.50,0.30,C和T等位基因分布频率分别为0.43,0.57和0.45,0.55,符合Hardy-Weinberg平衡.群体相关分析结果表明CYP11B2基因的C及T等位基因分布在高血压病组及正常人群差异无显著性(x2=4.838,P=0.89).然而女性高血压组CC基因型频率(0.24)较正常人群(0.12)高(x2=6.104,P＜0.05)结论CYP11B2基因T(-344)C多态性可能与新疆巴里坤哈萨克族女性高血压有关.     

原发性高血压伴肥胖患者血浆RAAS激素水平和CYP11B2－344C/T基因多态性的相关性

目的 通过检测原发性高血压伴肥胖患者血浆肾素-血管紧张素-醛固酮系统（RAAS）激素水平和醛固酮合成酶CYP11B2－344C/T基因多态性,探讨原发性高血压伴肥胖患者CYP11B2－344C/T易患基因型以及基因多态性与RAAS的关系。方法 随机选取1～2级原发性高血压患者60例,其中高血压伴肥胖者30例,单纯高血压者30例;同期体检中心体检者60例,其中单纯肥胖者30例,健康者30例。采用PCR-RFLP和琼脂糖凝胶电泳等方法检测CYP11B2－344C/T基因多态性,用放射免疫法检测血浆RAAS水平。结果 TT基因型例数与TC+CC基因型例数进行多重比较,有显著差异（P<0.05）,其中以原发性高血压伴肥胖组差异最为显著;T与C等位基因例数进行多重比较,有显著差异（P<0.05）,其中以原发性高血压伴肥胖组差异最为明显。按基因型分组统计分析各组血浆肾素、血管紧张素Ⅱ及醛固酮水平,TT基因型组显著高于TC、CC基因型组（P<0.05）。结论 原发性高血压伴肥胖患者CYP11B2－344C/T基因型以TT基因型为主,等位基因以T等位基因为主。TT基因型血浆RAAS激素水平各组份比TC、CC基因型显著升高,TT基因型可能为原发性高血压伴肥胖患者易感基因型。     

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。     

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     

醛固酮合成酶(CYP11B2)基因T(-344)C多态性与高血压病相关性研究

目的本研究探讨醛固酮合成酶基因(CYP11B2)基因T(-344)C多态性与原发性高血压之间关系.方法选取吉林省原发性高血压患者107例,其中男64例,女43例.正常人127例,其中男73例,女54例.排除高血压病及其它器质性疾病.所有研究对象用常规方法提取白细胞DNA.采用多聚酶链反应结合限制性内切酶(Hae Ⅲ)方法检测CYP11B2基因T(-344)C多态性.结果共扩增成功122例正常人和101例高血压患者DNA标本.原发性高血压组和正常对照组CYP11B2基因T(-344)C多态性基因型TT、CT、CC分布分别为6、28、67和5、59、58,其中C、T等位基因频率在两组分别为0.20、0.80和0.28、0.72.原发性高血压组TT基因型,T等位基因频率显著高于正常对照组,CT基因型,C等位基因频率显著低于正常对照组(P<0.05).结论本研究提示醛固酮合成酶基因(CYP11B2)基因T(-344)C多态性与中国人原发性高血压有关,可能是中国人原发性高血压的一个遗传标志.     

醛固酮合成酶基因-344C/T多态性与高血压左室肥厚相关性研究

目的观察醛固酮合成酶(CYP11B2)基因-344C/T多态性与高血压左室肥厚(LVH)的相关性。方法按心脏超声特点将314例原发性高血压患者分为左室肥厚[LVH(+)]组157例,无左室肥大[LVH(-)]组157例。使用常规方法提取白细胞DNA,采用多聚酶链式反应(PCR),限制性内切酶方法测定CYP11B2基因多态性。结果CYP11B2基因-344C/T多态性显示在LVH(+)组与LVH(-)组之间各基因型分布及等位基因频率显著不同,其中LVH(+)组TT基因型频率显著高于LVH(-)组(分别为0.66、0.51,P<0.01),而在CT基因型频率LVH(+)组显著低于LVH(-)组(分别为0.27、0.41,P<0.01);T等位基因频率LVH(+)组显著高于LVH(-)组(分别为0.79、0.72,P<0.05)。结论CYP11B2基因-344C/T多态性与高血压LVH密切相关,TT基因型频率和T等位基因频率可能是高血压LVH发生的机制之一。     

Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in patients with heart failure

We analyzed the possible association between aldosterone synthase (CYP11B2) T-344C polymorphism, which is associated with increased aldosterone activity, and the prevalence of atrial fibrillation (AF) in 196 consecutive patients who had symptomatic systolic heart failure (HF; left ventricular ejection fraction <40%) for > or =3 months before recruitment. Genomic DNA was extracted from peripheral blood leukocytes using a standard protocol. Subjects were genotyped for the CYP11B2 polymorphism using the polymerase chain reaction/restriction fragment length polymorphism approach. AF was present in 63 patients (33%) with HF. We found the -344 CC genotype to be a strong independent marker for AF. Almost 1/2 (45%) of patients with this genotype had AF compared with 1/4 (27%) with -344 TT and TC genotypes (p = 0.01). A multivariate stepwise logistic regression model that included age, gender, New York Heart Association class, CYP11B2 -344CC genotype, and echocardiographic measurements of left ventricular ejection fraction, left atrial dimension, left ventricular end-diastolic diameter, and mitral regurgitation severity showed that the CYP11B2 CC genotype (adjusted for age and left atrial size) was an independent predictor of AF (adjusted odds ratio 2.35, 95% confidence interval 1.57 to 3.51, p = 0.03). In conclusion, CYP11B2 T-344C promoter polymorphism predisposes to clinical AF in patients with HF.     

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。     

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。     

醛固酮合酶基因-344 C/T的多态性与心房颤动的关联研究

目的:探讨醛固酮合酶(CYP11B2)基因 -344 C/T的多态性与心房颤动(Af)的关系.方法:研究对象均来自湖北地区汉族人群,包括120例Af患者,120例非Af者.采用成组配比研究,取静脉血,提取基因组DNA,采用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)分析技术对2组人群CYP11B2基因-344 C/T的多态性进行分析.结果:CYP11B2 -344 CT+CC基因型频率在Af组与对照组之间差异有统计学意义(53.4%:37.5%,P=0.037),等位基因在2组间亦存在同样的趋势(C/T=28.8%:19.6%, P=0.019).单因素非条件Logistic回归分析CT+CC基因型频率患Af的危险性高(OR=1.82,95%CI 1.02～3.22, P=0.04), 排除混杂因素后, CT+CC基因型与人群患Af的风险呈弱相关(OR=1.73,95%CI 0.99～3.02,P=0.056);排除混杂因素后,左房内径与人群患Af的风险总是呈显著相关(OR=8.14,95%CI 3.43～19.31,P=0.000).结论:在湖北地区汉族人群中, CYP11B2 -344 C/T的点突变与Af的发病呈弱相关性,有可能是Af的遗传危险因素,左房内径的增加与Af的发病呈显著相关.     

Positive association of CYP11B2 gene polymorphism with genetic predisposition to essential hypertension

Predispositions to essential hypertension and cardiovascular diseases are possibly associated with gene polymorphisms of the renin-angiotensin system. Gene polymorphisms of angiotensinogen and angiotensin-converting enzyme genes have been suggested to be risk factors for hypertension and myocardial infarction. Concerning the polymorphism of aldosterone synthase (CYP11B2) gene, earlier studies have shown inconsistent results in terms of its relation to hypertension. In the present case-control study, we investigated the association of -344T/C polymorphism in the promoter region of human CYP11B2 gene with genetic predisposition to hypertension. The genotype of -344T/C polymorphism was determined in essential hypertension subjects (n=250) and normotensive subjects (n=221). The distributions of three genotypes (TT, TC, and CC) were significantly different between the hypertensive and the normotensive groups (chi(2)=9.61, P=0.008). Namely, the frequency of C allele was higher in the hypertensive patients than in the normotensive subjects (34.2 vs 26.5%, P=0.010). Our data suggest that the -344C allele of CYP11B2 gene polymorphism is associated with the genetic predisposition to develop essential hypertension.     

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.     

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。     

老年高血压患者血管紧张素转换酶和醛固酮合酶基因多态性与肾素血管紧张素醛固酮的关系

目的分析老年高血压晨峰患者血管紧张素转换酶(ACE)基因I/D、醛固酮合酶(CYP11B2)基因-344C/T多态性与肾素-血管紧张素-醛固酮系统(RAAS)的相关性。方法选择2016年2月~2017年12月云南省第一人民医院老年病科门诊及住院的老年原发性高血压患者200例,根据清晨血压水平分为晨峰增高组58例和非晨峰增高组142例。分析2组患者ACE基因I/D、CYP11B2基因-344C/T多态性和血浆RAAS参数的差异。结果 2组ACE基因型和等位基因频率比较,差异有统计学意义(χ^2=38.020,P=0.000;χ^2=42.040,P=0.000)。2组CYP11B2基因型和等位基因频率比较,差异无统计学意义(χ^2=0.261,P=0.878;χ^2=0.198,P=0.656)。晨峰增高组DD+TC、DD+TT基因型比例明显高于非晨峰增高组,差异有统计学意义(22.4%vs 3.5%,12.1%vs 2.1%,P<0.01);晨峰增高组II+TT、II+TC基因型比例明显低于非晨峰增高组,差异有统计学意义(13.8%vs 29.6%,P<0.05;5.2%vs 22.5%,P<0.01)。晨峰增高组血浆肾素、血管紧张素Ⅱ和醛固酮水平明显高于非晨峰增高组,差异有统计学意义(P<0.05,P<0.01)。logistic回归分析显示,DD+CC、DD+TC、DD+TT、肾素、血管紧张素Ⅱ为血压晨峰的重要影响因素(OR=8.084,95%CI:1.261~51.832,P=0.027;OR=14.459,95%CI:3.804~54.964,P=0.000;OR=9.753,95%CI:2.255~42.181,P=0.002;OR=1.816,95%CI:1.258~2.620,P=0.001;OR=0.634,95%CI:0.437~0.921,P=0.017)。结论 ACE基因DD型、肾素、血管紧张素Ⅱ是血压晨峰形成的主要影响因素。     

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.