醛固酮合酶基因多态性与原发性高血压相关性研究

目的探讨醛固酮合酶基因(CYP11B2)-344T/C多态性与原发性高血压的相关性。方法采用关联分析,收集湖南地区汉族男性原发性高血压患者100例,正常对照100名。应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对2组对象的CYP11B2-344T/C多态进行分析。结果2组对象CYP11B2基因型(TT型、CT型和CC型)的频率差异无统计学意义(χ2=0.34,P>0.05),等位基因的频率差异也无统计学意义(χ2=0.28,P>0.05),但各组内等位基因T的频率(原发性高血压组:67.67%)高于等位基因C(32.33%);对照组T69.67%高于C 30.33%。结论多基因联合分析显示,在男性患者中,CYP11B2-344T/C多态性与原发性高血压无明显相关,但CYP11B2-344各组内等位基因T的频率高于等位基因C。     

醛固酮合酶基因多态性与原发性高血压相关性研究

目的探讨醛固酮合酶基因（CYP11B2）-344T/C多态性与原发性高血压的相关性。方法采用关联分析,收集湖南地区汉族男性原发性高血压患者100例,正常对照100名。应用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对2组对象的CYP11B2-344T/C多态进行分析。结果2组对象CYP11B2基因型（TT型、CT型和CC型）的频率差异无统计学意义（χ^2=0.34,P〉0.05）,等位基因的频率差异也无统计学意义（χ^2=0.28,P〉0.05）,但各组内等位基因T的频率（原发性高血压组：67.67%）高于等位基因C（32.33%）;对照组T69.67%高于C 30.33%。结论多基因联合分析显示,在男性患者中,CYP11B2-344T/C多态性与原发性高血压无明显相关,但CYP11B2-344各组内等位基因T的频率高于等位基因C。     

心脏再同步治疗反应性与β受体阻滞剂及血管紧张素转化酶抑制剂的关系

目的：分析心脏再同步治疗(CRT)患者术后药物治疗情况及与 CRT 反应性的关系。方法行 CRT 的慢性心力衰竭患者35例,平均年龄(64.1±9.7)岁;所有患者术前及术后6个月均行常规超声心动图检查,并根据临床表现评估术前及术后6个月患者心功能分级。对患者 CRT 植入前后药物治疗情况,尤其是β受体阻滞剂及血管紧张素转化酶抑制剂(ACEI)的使用情况进行分析。根据 CRT 术后反应性分为有反应组及无反应组,对两组β受体阻滞剂及 ACEI 术前和术后使用情况进行比较,分析 CRT 反应性与药物剂量变化的关系。结果 CRT 临床有反应组28例,无反应组7例。有反应组术前和术后美托洛尔平均使用剂量分别为(25.0±11.0)mg/d 和(59.6±24.4)mg/d (P <0.01),而无反应组术前和术后美托洛尔平均使用剂量分别为(25.0±8.8)mg/d 和(27.5±22.4)mg/d(P >0.05)。CRT 治疗有反应组术前和术后培哚普利日平均使用剂量分别为(3.47±0.91)mg/d 和(4.74±1.52)mg/d (P <0.05),而无反应组术前和术后培哚普利日平均使用剂量分别为(3.60±0.89)mg/d 和(3.80±0.45)mg/d(P >0.05)。CRT 术后反应性与 CRT 治疗前后β受体阻滞剂剂量变化有较好的相关性(r =0.688,P <0.01),而与ACEI 剂量变化无明显相关性(r =0.355,P >0.05)。结论 CRT 反应性与术后优化药物治疗相关,其治疗效果是优化药物治疗及起搏器治疗的共同作用结果。     

血管紧张素转换酶基因多态性与肝肾综合征相关研究

目的　探讨血管紧张素转换酶 (ACE)基因插入 /缺失 (I/ D)多态性与失代偿性肝硬化并发肝肾综合征 (HRS)之间的关系。方法　应用聚合酶链反应方法扩增 5 6例失代偿性肝硬化并发 HRS患者及 6 0例正常对照组 ACE基因上 DNA片断 ,根据 I/ D判断其多态性 ;同时各例均采血测丙氨酸转氨酶、天冬氨酸转氨酶、血清肌酐 (SCr)及尿素氮 (BU N)等指标 ,并测定肾小球滤过率 (GFR) ,比较不同基因型间上述指标的差异显著性。结果　 HRS患者各基因型及等位基因频率与对照组间差异均无显著性 (P均 >0 .0 5 ) ;I等位基因频率均显著高于 D等位基因频率 (P均 <0 .0 1)。正常对照组中 3种基因型频率间差异无显著性 (P>0 .0 5 ) ;HRS组中 II基因型频率显著高于 ID型及 DD型 (P均 <0 .0 5 )。 II基因型的 BU N与 SCr均显著高于 ID型及 DD型(P均 <0 .0 5 ) ,GFR显著低于 ID型及 DD型 (P均 <0 .0 5 )。结论　 ACE基因多态性与失代偿性肝硬化并发HRS的发生率有关 ,II基因型可能为失代偿性肝硬化易并发 HRS的遗传学方面因素 ;失代偿性肝硬化并发HRS患者中 ,II基因型个体的肾功能衰竭程度重于 ID型及 DD型。     

Pharmacokinetic interaction between cefdinir and two angiotensin-converting enzyme inhibitors in rats.

The pharmacokinetic interaction between cefdinir and an angiotensin-converting enzyme inhibitor (captopril or quinapril) was investigated in rats. The linearity of cefdinir pharmacokinetics was demonstrated in three groups of rats receiving 10, 20, or 40 mg of cefdinir per kg of body weight intravenously. Then, three other groups of rats were established as follows: group 1 (n = 5) received cefdinir (10 mg/kg) intravenously, and 12 blood samples per rat were drawn between 0 and 8 h after injection of the dose; group 2 (n = 5) was treated in the same way as group 1, but captopril (0.8 mg/kg) was coadministered by intraintestinal injection into all animals; group 3 (n = 6) was treated in the same way as group 2, but quinapril (0.8 mg/kg) replaced captopril. Plasma cefdinir concentrations were measured by liquid chromatography, and the data were analyzed by a noncompartmental method. Finally, three groups of four or five rats each were set up as described above, but the cefdinir dose was 20 mg/kg and the animals were sacrificed 1 h after drug injection to collect blood to determine the unbound cefdinir fraction (fu) by ultrafiltration. The angiotensin-converting enzyme inhibitors increased the mean cefdinir area under the concentration-time curve up to 8 h by a factor of 1.8 (captopril; P < 0.05) and a factor of 3.5 (quinapril; P < 0.05). With captopril, mean cefdinir clearance was decreased by a factor of 2, and the volume of distribution increased by the same factor, while the fu increased from 15.4% +/- 3.0% (cefdinir alone) to 22.8% +/- 10.9% (cefdinir plus captopril). Captopril increased the cefdinir half-life from 0.62 +/- 0.17 to 2.92 +/- 0.95 h. With quinapril, the interaction was so strong that no elimination phase was detectable in four of the six rats, and therefore, no pharmacokinetic parameter values other than the cefdinir fu could be calculated; the cefdinir fu increased to 25.1% +/- 11.1%. It is concluded that captopril and quinapril (and/or their metabolites) have a major impact on the disposition of cefdinir in rats, probably by competition at the plasma protein-binding level and at the tubular anionic carrier level. This latter mechanism should also be relevant in humans.     

荧光PCR检测CYP2C19基因分型与氯吡格雷临床疗效的相关性研究

目的通过分析CYP2C19基因型与ADP抑制率之间的关系,探讨CYP2C19基因分型与氯吡格雷抗凝治疗效果的关系。方法选取急性冠脉综合征（ACS）并成功接受经皮冠状动脉介入治疗术（PCI）的患者55例,收集患者EDTA抗凝静脉血提取血液基因组DNA,用实时荧光PCR方法分析CYP2C19基因型,测定每名患者ADP抑制率,用统计学方法分析CYP2C19不同基因型患者ADP抑制率的差异。结果所有入组患者根据基因型不同分为快代谢组占49.09%（27/55）,中等代谢组占38.19%（21/55）,慢代谢组占12.73%（7/55）。三组ADP抑制率比较,两两相比差异均有统计学意义（P〈0.01）。结论 CYP2C19基因多态性与氯吡格雷抵抗存在关联,快代谢型患者PCI术后服用氯吡格雷疗效好于携带基因突变的患者,慢代谢型患者PCI术后服用氯吡格雷疗效差。     

Racial differences in blood pressure response to angiotensin-converting enzyme inhibitors in children: a meta-analysis

Angiotensin-converting enzyme (ACE) inhibitors are frequently used to treat hypertension in children.(1) ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and cardiac hypertrophic properties of angiotensin II and the vasodilatory and natriuretic properties of bradykinin; they also alter the metabolism of other vasoactive substances.(2) Through these mechanisms, ACE inhibitors decrease systemic vascular resistance and promote natriuresis without increasing heart rate. This study evaluated the results of six trials of ACE inhibitors in children, using meta-analytic techniques to estimate the effect of race on blood pressure response.     

2型糖尿病患者脂蛋白酯酶、血管紧张素转换酶及载脂蛋白-E基因多态性与冠心病的关系

目的　探讨 2型糖尿病患者脂蛋白酯酶 (LpL)、血管紧张素转换酶 (ACE)及载脂蛋白 E(ApoE)基因与冠心病的关系。方法　采用聚合酶链反应 限制性片段长度多态性 (PCR PFLP)、聚合酶链反应 (PCR)和聚合酶链反应 等位基因特异性寡核苷酸 (PCR ASO)探针杂交技术分别检测 2型糖尿病并冠心病组及对照组LpL、ACE、ApoE基因型。结果　① 2型糖尿病并冠心病组LpL/P P 及P 频率分别为 18.2 %和 4 2 .9% ,高于对照组 (9.5 %和 32 .5 % ) ,但差异无统计学意义 (P >0 .0 5 )。LpL/HindⅢ多态性频率分布两组间无明显差异 (P >0 .0 5 )。② 2型糖尿病组ACE/DD及D频率分别为 33.8%和 5 7.1% ,明显高于对照组(12 .7%和 36 .5 % ) (P <0 .0 1)。③ 2型糖尿病并冠心病组ε 3/ 3和ε 4 / 3频率分别为 5 4 .8%和 31.2 % ,分别明显低于 (ε 3/ 3)和高于 (ε 4 / 3)对照组 (76 .19%和 11.11% ) (均为P <0 .0 1)。ε 4等位基因频率为 2 0 .8% ,明显高于对照组 (9.5 2 % ) (P =0 .0 1)。结论　LpL/ p 、ACE/D及ApoE/ε 4等位基因增高 2型糖尿病并发冠心病患者的遗传易感性。     

血管紧张素转换酶和内皮型一氧化氮合酶基因多态性与高血压的相关性

目的探讨血管紧张素转换酶(ACE)基因I/D、内皮型一氧化氮合酶 (eNOS)基因G894T多态性与原发性高血压(EH)的关系.方法采用基因芯片技术检测 224例(124例高血压患者和100例健康人)ACE和eNOS基因多态性.结果 EH组ACE DD基因型携带者频率显著高于对照组 (30.65% vs16.00%,P<0.05 ),eNOS- GT TT基因型频率与对照组相比无显著性差异( 12.90% vs 15.00%,P＞0.0 5).结论 ACE-DD基因多态性可能是高血压病的独立危险因素,eNOS基因G894T多态性可能不是高血压病的独立危险因素.基因芯片技术为研究多种易感基因与高血压病的相关性提供了一项高效、敏感的方法.     

蒙古族人群血管紧张素转换酶基因多态性与高血压的关系

背景有关血管紧张素转换酶基因多态性与高血压关系的研究已有报道,但在蒙古族人群中尚不十分清楚.蒙古族是高血压患病率较高的民族,因此有必要探讨蒙古族人群中血管紧张素转换酶基因多态性与高血压的关系.目的探讨蒙古族人群血管紧张素转换酶基因多态性与高血压的关系.设计采用现况调查的方法.地点和对象选择内蒙古自治区通辽市科左后旗朝鲁吐苏木作为本研究现场,所有研究对象均为在此长期居住的蒙古族居民.共获得有高血压家族史的高血压者51例、血压正常者32例和没有高血压家族史的高血压者64例、血压正常者85例.干预应用聚合酶链式反应检测血管紧张素转换酶基因的插入/缺失多态性.主要观察指标血管紧张素转换酶多态性基因型频率和I、D等位基因频率.结果血管紧张素转换酶基因的三种基因型(II,ID,DD)在4组人群间的分布差异无显著性意义(P＞0.1).在4组人群中均表现出ID基因型频率最高,其次为Ⅱ基因型,DD基因型频率最低.I,D等位基因在4组人群间的分布也差异无显著性意义(P＞0.1).在4组人群中I等位基因频率均高于D等位基因频率.结论血管紧张素转换酶基因I/D多态性与蒙古族高血压的发生无关联.     

Recent developments in the design of angiotensin-converting enzyme inhibitors

Orally-active angiotensin-converting enzyme inhibitors are rapidly establishing themselves in the therapy of hypertension and congestive heart failure. Concerted efforts in a number of laboratories have now led to the discovery or synthesis of an unparalleled variety of potent inhibitors. The manner in which several of these inhibitors bind to ACE is beginning to be understood. It is hoped that some of the insights to be derived from the SAR and structural studies done with ACE inhibitors will be applicable to other enzyme targets as well. The success of ACE inhibitors as pharmacological tools and in the clinic will also quite certainly encourage future efforts to develop new enzyme inhibitor approaches to drug therapy.     

Biliary excretion and conjugation of diacid angiotensin-converting enzyme inhibitors

The metabolism and biliary excretion of the diacid angiotensin-converting enzyme inhibitors enalapril, lisinopril, perindopril and ramipril have been studied in an isolated perfused rat liver model. Inhibitors were presented to the livers at a dose of 100 micrograms. The hepatic clearance of lisinopril was very low (0.072 ml/min) and was hardly excreted into the bile. The clearances of enalapril, perindopril and ramipril were higher at 0.63, 0.87 and 9.9 ml/min, respectively, and were excreted into bile. The amounts of ester prodrugs excreted in bile were 4.0, 6.1 and 14%, respectively, whereas the diacid forms were excreted to the extent of 46, 27 and 71% of the administered dose, respectively, over 4 hr. Glucuronide metabolites were only detected in bile in significant concentrations for perindopril and ramipril. Base hydrolysis of the perfusate samples showed that lisinopril was not significantly metabolized to conjugates and that little metabolism of enalapril occurred other than rapid conversion to the diacid form. However, both perindopril and ramipril were extensively metabolized beyond the diacid form. These differences in hepatic handling can in part be explained by their octanol-buffer partition coefficients but may also be related to the introduction of a bicyclic ring in perindopril and ramipril which increases their ability to be metabolized and excreted into bile. These differences in hepatic handling of angiotensin-converting enzyme are likely to influence their clinical usefulness, particularly in renal and hepatic disease.     

Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy

ABCC2 (MRP2, cMOAT) expression has been implicated in cisplatin resistance in vitro. In mice, cisplatin disposition and toxicity were unaffected by Abcc2 knockout (Abcc2?/?). Moreover, in cancer patients (n = 237), cisplatin pharmacokinetics (P > 0.12) and efficacy (P > 0.41) were not associated with seven of the single-nucleotide polymorphisms (SNPs) in ABCC2. These SNPs were also not correlated with ABCC2 expression in the NCI60 panel (P > 0.26) or with cisplatin-induced cytotoxicity (P = 0.21). These findings highlight the importance of verifying drug-transporter interactions with in vitro tests in humans.     

醛固酮合成酶CYP11B2基因多态性与中国汉族人原发性高血压关系的系统分析

目的 Meta分析中国汉族人醛固酮合成酶CYP11B2基因多态性与原发性高血压关系。方法 查阅1980年1月至2006年7月发表的有关醛固酮合成酶CYP11B2基因多态性与原发性高血压关系的病例对照试验研究文献，选择的数据库有中国生物医学文献数据库（CBMdise）、中国学术期刊全文数据库（CAJ—CD）和Medline。以原发性高血压组和健康对照组基因分布的OR值为统计量，全面检索相关文献并剔除不符合要求的文献，排除发表偏倚的影响。应用RevMan4．2软件对各研究结果进行一致性检验和数据合并。最终入选5篇随机对照试验文献。结果 5．篇文献的病例对照试验一致性较好，原发性高血压组总计高血压患者1000例，对照组967例，原发性高血压组与对照组TT/（TC＋CC）OR值（95％可信区间）0．95（0．79，1．13），显著性检验Z值为0．60，P=0．55。T等住基因频率OR值为（95％可信区间）0．92（0．80，1．06），显著性检验Z值为1．17，P=0．24。结论 中国汉族人醛固酮合成酶CYP11B2基因多态性与原发性高血压无关。     

Associations of CYP2B6 genetic polymorphisms with Hirschsprung’s disease in a southern Chinese population

BackgroundHirschsprung’s disease (HSCR) is an enteric nervous system birth defect partially caused by a genetic disorder. Single‐nucleotide polymorphisms (SNPs) of the cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene are reported to be associated with HSCR.MethodsWe evaluated the association of rs2054675, rs707265, and rs1042389 with HSCR susceptibility in southern Chinese children including 1470 HSCR patients and 1473 controls using the TaqMan SNP Genotyping Assay.Resultsrs2054675 C allele and the rs707265 G allele were risk SNPs for total colonic aganglionosis (OR = 1.82, 95% CI 1.29 ~ 2.55, P_adj < 0.001 and OR = 0.68, 95% CI 0.48 ~ 0.97, P_adj = 0.034). These results suggested that CYP2B6 rs2054675 and rs707265 polymorphisms were associated with increased susceptibility to the severe HSCR subtype in southern Chinese children.ConclusionWe suggest that CYP2B6 rs2054675 and rs707265 polymorphisms are associated with increased susceptibility to the severe HSCR subtype in southern Chinese children.     

Association between COVID-19 and angiotensin-converting enzyme inhibitors with the spotlight on zinc: an opinion

In the setting of the raging COVID-19 pandemic, the search for innovative therapeutics is desperately sought after. As we learn more about the characteristics and metabolic health of patients and as our understanding of COVID-19 pathophysiology and treatment progresses, so is our understanding of medication effects that might increase disease severity. As of late, ACE inhibitors have been under investigation for a potential increase in illness severity due to ACE2 upregulation. Given our knowledge of other nutrient-pharmaceutical interactions, could the ACE inhibitor impact on COVID be due to something else? In this paper, we discuss the possibility that ACE inhibitors might be affecting COVID-19 patients by causing zinc insufficiency.

KEY MESSAGES

1. Zinc deficiency caused by chronic ACE inhibitor usage may exacerbate the pathogenicity of COVID-19 in susceptible patients.
2. A multi-center study is needed to assess the zinc levels of patients with COVID-19 who are taking ACE inhibitors and other medications that may result in low zinc levels.