内皮型一氧化氮合酶基因G894T多态性与冠心病的相关性研究

目的 探讨内皮型一氧化氮合酶(eNOS)基因G894T多态性与冠心病(CHD)的发生及其严重程度间的关系.方法 根据冠状动脉造影结果选取洛阳地区汉族居民CHD患者203例(CHD组)和正常对照组194例,以冠状动脉病变支数判定严重程度.应用聚合酶链式反应-限制性片段长度多态性分析法(PCR-RFLP)检测eNOS基因G894T多态性,分析G894T多态性与CHD的关系.结果 CHD组GT+TT基因型分布与T等位基因频率均明显高于对照组,差异有统计学意义(P＜0.05);CHD组eNOS基因型分布在单支与多支病变组间差异无统计学意义(P＞0.05).结论 eNOS基因894位点G→T突变与洛阳地区汉族人群CHD的发生相关联,但与其严重程度间无关联.     

内皮型一氧化氮合酶基因多态性与原发性高血压的关系研究

目的:探讨天津市汉族人群内皮型一氧化氮合酶(eNOS)基因G894T和27 bp数目可变的串联重复序列(VNTR)多态性与原发性高血压的关系.方法:对500例研究对象根据血压分为原发性高血压组350例和对照组150例,采用PCR-RFLP对2组eNOS第7外显子G894T及第4内含子VNTR进行基因多态性分型.分析不同基因型与高血压发病的关系.结果:(1)2组eNOS G894T位点2组基因型和基因频率差异无统计学意义(P＞0.05).(2)高血压组eNOS第4内含子VNTR aa+ab基因型及a等位基因频率高于对照组(P＜0.05).(3) eNOS基因G894T和第4内含子VNTR对高血压的发生无协同作用.结论:eNOS基因G894T多态性与原发性高血压无关,而第4内含子VNTR多态性与原发性高血压存在相关性,两者无协同作用.     

内皮型一氧化氮合酶基因G894T多态性与冠心病的相关性研究

目的探讨内皮型一氧化氮合酶(eNOS)基因G894T多态性与冠心病(CHD)的发生及其严重程度间的关系。方法根据冠状动脉造影结果选取洛阳地区汉族居民CHD患者203例(CHD组)和正常对照组194例,以冠状动脉病变支数判定严重程度。应用聚合酶链式反应-限制性片段长度多态性分析法(PCR-RFLP)检测eNOS基因G894T多态性,分析G894T多态性与CHD的关系。结果 CHD组GT+TT基因型分布与T等位基因频率均明显高于对照组,差异有统计学意义(P<0.05);CHD组eNOS基因型分布在单支与多支病变组间差异无统计学意义(P>0.05)。结论 eNOS基因894位点G→T突变与洛阳地区汉族人群CHD的发生相关联,但与其严重程度间无关联。     

ecNOS基因多态性与2型糖尿病心血管危险因素集簇的关系

目的：探讨内皮固有型一氧化氮合酶（ecNOS）基因G894T多态性与天津市汉族成年2型糖尿病（T2DM）患者心血管危险因素集簇的关联性。方法：随机抽取无心血管病并发症且无血缘关系的天津市汉族成年T2DM患者80例，静脉血提取基因组DNA，用聚合酶链反应-限制片段长度多态性（PCR—RFLP）法检测ecNOS基因G894T多态性。结果：（1）ecNOS基因第7外显子894位点基因型分布为GG基因型63例（78．75％）、GT基因型17例（21．25％）和TT基因型0例；（2）GG与GT基因型患者的各项临床及实验室指标差异均无统计学意义。（3）随着T2DM患者存在心血管危险因素的增多，GT基因型患者的比例逐渐升高，差别具有统计学意义（x^2=7．544，P〈0．05）。结论：ecNOS基因G894T多态性与T2DM患者心血管危险因素的集簇存在关联性．     

内皮型一氧化氮合酶基因多态性与老年高血压关系的研究

目的:探讨内皮型一氧化氮合酶(eNOS)基因894G/T多态性与老年人原发性高血压病(EH)之间的关系。方法:应用聚合酶链反应限制性片段长度多态性技术对湖北地区汉族129例高血压病患者(EH组)和117例健康者(NT组)的eNOS外显子894位点进行基因分型,生化技术测定其血脂水平。结果:EH组T等位基因频率以及GT+TT基因型分布频率均显著高于NT组(P<0.05);在年龄不同组中这种显著相关性仅存在年龄小于61岁的中青年患者中。结论:eNOS基因可能与老年人群原发性高血压发生无关。     

一氧化氮合酶基因多态性与脑梗塞的关系

脑血管病是多基因、多因素疾病,一氧化氮合酶基因是研究的主要侯选基因。人类内皮型一氧化氮合酶（eNOS）基因位于第7号染色体7q35-36区,为单拷贝基因．全长约21kb,含26个外显子及25个内含子。孙晓红等报道Marsden在1993年首先发现eNOS基因外显子7上894位核苷酸存在G-T的突变位点,从而使298位编码蛋白出现谷氮酸由天冬氮酸替代（Glu→Asp）。G894T突变构成2种等位基因G和T,3种基因型GG、GT和TT。国内外研究结果也认为eNOS基因外显子7的第894位核苷酸多态性．影响了eNOS酶自身的功能活性。     

内皮型一氧化氮合酶基因G894T多态性与ACEI降压疗效相关性研究

目的探讨原发性高血压患者内皮型一氧化氮合酶基因(eNOS)G894T多态性与血管紧张素转换酶抑制剂(ACEI)降压疗效之间的关系。方法 281例1-2级原发性高血压患者经安慰剂治疗2周后,血压符合入选标准者分别给予咪达普利5～10mg/d或贝那普利10～20mg/d,治疗6周。用酚-氯仿法提取基因组DNA,采用PCR结合限制性内切酶片段长度多态性(RFLP)方法检测eNOS基因型,分析不同基因型组与ACEI降压疗效的关系。结果本研究中eNOS 3种基因型频率分别为GG66.2％、GT27.8％、TT6.0％,等位基因G、T的频率分别为0.80和0.20。ACEI治疗后,eNOS基因GG、GT、TT组收缩压下降值分别为(14.51±11.19)mmHg,(16.11±12.31)mmHg,(12.38±14.30)mmHg;舒张压下降值分别为(8.95±6.56)mmHg,(9.00±6.92)mmHg,(9.37±4.80)mmHg,3组间收缩压与舒张压下降值均无统计学差异。结论 eNOS基因G894T多态性与ACEI降压疗效无关。     

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推荐人:张建平中山大学附属第二医院妇产科教授、主任医师推荐文章《:一氧化氮合酶基因多态性与妊娠高血压综合征的关系》,《中华围产医学杂志》2005年第8卷第2期。作者:蔡霞,等。新疆医科大学附属第一医院产科。摘要:目的:探讨一氧化氮合酶基因(eNOS)第7外显子G894T点突变与妊娠高血压综合征(妊高征)的关系。方法:应用聚合酶链反应限制性片段长度多态性(PCRRFLP)技术检测了66例妊娠晚期妊高征患者(妊高征组)和91例正常晚期妊娠妇女(对照组)的eNOS基因多态性位点频率。结果:妊高征组eNOS基因型频率:野生型(GG)、杂合子(GT)、突变纯…     

IL-4受体基因多态性与儿童过敏性紫癜肾炎的相关分析

目的探讨IL-4受体基因多态性与儿童过敏性紫癜肾炎（HSPN）的关系。方法采用聚合酶链反应-限制性酶切多态性方法检测131例HSPN组患儿和120例健康对照组儿童的IL-4Rα亚单位Q576R位点基因多态性。结果 HSPN组IL-4Rα亚单位QR＋RR基因型和R576等位基因频率均高于对照组（P〈0.05）。结论 IL-4Ra亚单位R576可能是HSPN患儿的危险因子。     

内皮细胞固有型一氧化氮合成酶基因G894T变异与糖尿病肾病的关系

目的：观察内皮细胞固有型一氧化氮合成酶（ecNOS）基因外显子7的Glu298Asp基因多态性与2型糖尿病肾病（DN）的关系。方法：利用聚合酶链反应限制性片段长度多态性（PCR-RFLP）技术检测了天津地区299例2型糖尿病患者和100例正常对照者的ecNOS基因外显子7的基因型，比较各组间的等位基因频率与基因型频率。结果：（1）2型糖尿病合并持续性微量白蛋白尿组（DN1组）的GT基因型和T等位基因频率高于糖尿病非肾病组（DM组）和正常对照组（C组），差异有统计学意义（P〈0．05）。（2）在2型糖尿病患者中GT基因型者较GG基因型者的DN患病率高（X^2=5．252，P=0.022）。（3）高血压、血纤维蛋白原（FIB）、ecNOS外显子7的GT基因型是2型糖尿病合并DN的独立危险因素。（4）2型糖尿病合并高血压组（DMEH组）、糖尿病非高血压组（DM1组）和C组间ecNOS基因外显子7的基因型分布和等位基因频率差异无统计学意义（P〉0．05）。结论：ecNOS基因外显子7的基因G894T（Glu298Asp）的变异可能是天津地区2型糖尿病患者DN易感性的基因标志之一，可能参与DN的启动；该基因多态性不是通过促进高血压的发生而增加DN的易感性。     

G894T polymorphism of eNOS gene is a predictor of response to combination of inhaled corticosteroids with long-lasting β(2)-agonists in asthmatic children

Aim: Nitric oxide synthase enzymes have an important role in airway inflammation in asthmatic children. In the present study, the association between eNOS gene polymorphisms and response to inhaled corticosteroids (ICS) and long-lasting β(2)-agonists (LABAs) was investigated. Patients & methods: A total of 81 asthmatic children treated with ICS plus LABAs and 96 healthy controls were genotyped for eNOS G894T and -786T/C polymorphisms and their haplotypes using the PCR-RFLP method. Results: G894T and -786T/C polymorphisms were not associated with asthma susceptibility. Among asthmatic children, 894TT carriers had higher change in forced expiratory volume in 1 s (FEV(1)) in response to ICS plus LABAs compared with 894GG carriers (21.9 ± 3.8 vs 1.6 ± 1.9%; p < 0.001). In responders (FEV(1) change ≥7.5%), frequency of 894TT genotype was significantly higher than in nonresponders (26.2 vs 2.6%, p < 0.001). Results for the -786T/C polymorphism alone were less clear and in most cases nonsignificant. Conclusion: The G894T polymorphism was associated with response to ICS and may serve as a useful pharmacogenetic marker of response to ICS plus LABAs in asthmatic children. Original submitted 10 May 2012; Revision submitted 13 July 2012.     

Impact of the endothelial nitric oxide synthase gene G894T polymorphism on renal endothelial function in patients with type 2 diabetes

OBJECTIVE: Endothelial dysfunction and increased oxidative stress contribute to the progression of diabetic nephropathy. To analyze the functional significance of the G894T polymorphism of NOS3, the gene encoding endothelial nitric oxide synthase (NOS), we assessed basal nitric oxide activity and the amount of oxidative stress in the renal circulation of patients with type 2 diabetes. METHODS: Renal plasma flow (RPF) was assessed by steady-state input clearance technique with sodium para-aminohippurate in 84 patients with type 2 diabetes and 84 patients without diabetes. RPF was measured at baseline and after the infusion of the NOS inhibitor N-monomethyl-L-arginine (4.25 mg/kg); the substrate of NOS L-arginine (100 mg/kg); and coinfusion of vitamin C (3 g) with L-arginine (100 mg/kg). RESULTS: The decrease of RPF to N-monomethyl-L-arginine was similar between carriers of the T allele and homozygous carriers of the G allele in patients with diabetes (-56+/-40 vs. -68.1+/-74 ml/min/1.73 m, P=0.342) and patients without diabetes (-66.7+/-81 vs. -58.3+/-63 ml/min/1.73 m, P=0.606). In patients with diabetes, however, carriers of the T allele revealed a more pronounced increase of RPF to coinfusion of vitamin C with L-arginine than homozygous carriers of the G allele (61.8+/-75 vs. 22.3+/-73 ml/min/1.73 m, P=0.021), whereas in patients without diabetes the response of RPF to coinfusion of vitamin C with L-arginine was similar between both groups (46.2+/-80 vs. 70.7+/-86 ml/min/1.73 m, P=0.217). Gene-environment interaction between disease (diabetes) and genotype (genotype GG vs. genotype GT/TT) was observed for increase of RPF to coinfusion of vitamin C with L-arginine (P=0.020). CONCLUSION: G894T polymorphism of NOS3 has no impact on the basal nitric oxide activity of renal circulation. In contrast, the T allele is associated with increased oxidative stress in the renal circulation in patients with diabetes suggesting a specific role of the G894T polymorphism in the pathogenesis of diabetic nephropathy.     

Heterogeneity in hand veins responses to acetylcholine is not associated with polymorphisms in the G-protein beta3-subunit (C825T) and endothelial nitric oxide synthase (G894T) genes but with serum low density lipoprotein cholesterol.

Vascular responses to acetylcholine (ACh) are notoriously variable, the reason for this phenomenon is unknown. We tested the hypothesis that the variability in venous response to acetylcholine may be associated with two recently identified genetic polymorphisms for proteins involved in the signal transduction pathway, i.e. the G-protein beta3-subunit (GNB3) and endothelial nitric oxide synthase (eNOS). The dorsal hand vein technique was used in 37 healthy subjects. Hand veins were preconstricted with the alpha1-adrenoceptor agonist phenylephrine and the venodilator response to local ACh infusion was measured with and without comedication of acetylsalicylic acid or co-infusion of N(G)-monomethyl-L-arginine (L-NMMA). In addition, all subjects received routine laboratory tests and 26 of them were genotyped for the C825T polymorphism of the GNB3 gene and for the G894T polymorphism of the eNOS gene. A striking variability in venous response to ACh was found with dilation observed in the low ACh concentration range and reduced dilation or even constriction at high concentrations. ACh-induced venodilation was mediated by muscarinic receptors and abolished in the presence of both acetylsalicylic acid and L-NMMA suggesting dependence on endothelium. We did not find any association of the variability in ACh response with GNB3 or eNOS allele status. On the other hand, a significant positive correlation between ACh responsiveness and low density lipoprotein-cholesterol status was detected. Two recently discovered gene polymorphisms are not responsible for the profound heterogeneity in venodilator response to ACh. Surprisingly, this variability appears to relate to the lipid status of the subjects. The exact nature of this new finding requires further study.     

Functional effects of endothelial nitric oxide synthase genetic polymorphisms on haemorheological parameters in healthy human individuals

The constitutive endothelial nitric oxide synthase (eNOS) plays a major role in circulatory homoeostasis and shows genetic polymorphism. eNOS is expressed and functional in blood cells, including erythrocytes. There is limited knowledge about the consequences of eNOS genetic variability in haemorheological parameters and erythrocyte functioning. The purpose of this study was to investigate the effects of three eNOS genetic polymorphisms, namely exonic G894T (Glu298Asp), intronic VNTR (27-bp repeat) and 5'-flanking T(-786)C polymorphisms on haemorheological variables, such as erythrocyte deformability and erythrocyte aggregation (rouleaux formation) in healthy non-smoking volunteers. Sixty subjects (19 women, 41 men) were examined for genotypes and haemorheological variables. Genotypes were determined by polymerase chain reaction and restriction analysis. Haemorheological variables were measured by means of a laser-assisted optical rotational cell analyser (LORCA). Erythrocyte aggregation was significantly decreased in individuals with 894TT genotype when compared to subjects with the (G) allele. Aggregation indices (AI) were 54.7±3.2% versus 61.0±0.9% (p=0.026), and the half-lives (t(1/2) ) for aggregation formation were 3.43±0.43 versus 2.55±0.12 sec. (p=0.024), respectively. Similarly, VNTR-bb genotype significantly altered erythrocyte aggregability. AI values were 58.7±1.1% in subjects with VNTR-a allele versus 63.7±1.2% in subjects with bb genotype (p=0.011); t(1/2) values were 2.86±0.16 versus 2.20±0.13 sec., respectively (p=0.016). T(-786)C polymorphism did not change any haemorheological parameters. These findings suggest that eNOS 894TT genotype is associated with decreased erythrocyte aggregation, while VNTR-bb genotype increases aggregability in healthy human individuals. eNOS genetic variants may contribute in the pathogenesis of microvascular disorders by altering erythrocyte functions in human beings.     

血府逐瘀汤加味治疗过敏性紫癫120例临床研究

目的观察探讨血府逐瘀汤加味治疗过敏性紫癫的临床疗效。方法选我院2009年3月至2011年3月期间收治的过敏性紫癫患者217例,随机分为观察组120例和对照组97例,观察组使用血府逐瘀汤加味治疗,对照组使用西医治疗,观察对比两组的治疗效果。结果观察组无不良反应,总有效率为96.7%,对照组不良反应有11例占11.3%,总有效率为70.1%,两组疗效比较差异显著(P<0.05),具有统计学意义。结论使用血府逐瘀汤加味治疗过敏性紫癫的效果显著,无不良反应,对治疗过敏性紫癫具有重要的临床应用价值。     

eNOs基因T786C多态性与原发性高血压的关系

目的:探讨内皮型一氧化氮合酶(eNOs)基因T786C多态性与原发性高血压的关系。方法:选取原发性高血压患者266例(高血压组)和健康人群100例(对照组),入院后空腹12h抽取肘正中静脉血4mL,常规测定生化及凝血功能等各项指标。进行eNOs基因T786C的PCR扩增、酶切和基因型分析。分析不同基因型与高血压发病的关系。结果:高血压组的年龄、收缩压、舒张压、体质量指数及有饮酒史者均高于对照组,差异均有统计学意义(P<0.05或P<0.01);其他指标比较差异无统计学意义(P>0.05)。2组TT、TC及CC基因型分布和T、C等位基因频率分布差异均无统计学意义(P>0.05)。高血压组患者中C等位基因携带者的收缩压及舒张压与TT基因型者差异无统计学意义(P>0.05)。影响高血压的因素有年龄、性别和体质量指数。结论:eNOs基因T786C多态性在高血压发病中不起直接作用,可能通过影响相关危险因素参与高血压发病。     

In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism.

Endothelial nitric oxide synthase catalyses the formation of the vasodilator nitric oxide, a major regulator of vascular tone. The Asp298 polymorphism of the nitric oxide synthase gene is associated with altered function and expression of the enzyme in vitro and myocardial infarction and coronary artery spasm in vivo. We examined the effect of the Glu298Asp polymorphism on: (1) local vascular responses to phenylephrine, acetylcholine, glyceryl trinitrate and prostaglandin E1 in the dorsal hand vein; (2) changes in forearm blood flow during mental stress, a measure of nitric oxide-mediated effect on resistance vessels; (3) excretion of urinary nitrite/nitrate as a measure of total body nitric oxide production; and (4) F2-isoprostane metabolite, a measure of oxidative stress, in healthy Glu298 (n = 12) and Asp298 (n = 13) homozygotes. There were no significant differences in acetylcholine dose responses (P = 0.29) in Glu298 and Asp298 homozygotes. Responses to glyceryl trinitrate, prostaglandin E1 and the alpha-adrenergic agonist phenylephrine did not differ by genotype. Forearm blood flow was similar at rest and increased significantly (from 7.5 ml/min/100 ml to 12.2 ml/min/100 ml; P = 0.003), but similarly (P = 0.2), during mental stress in both genotypes. Asp298 homozygotes excreted significantly less nitrate/nitrite than Glu298 homozygotes (nitrate + nitrite/creatinine ratio 0.05 +/- 0.01 vs. 0.09 +/- 0.01, respectively; P < 0.005). Urinary F2-isoprostane metabolite excretion did not differ (Glu298, 2.04 +/- 0.25 ng/mg creatinine; Asp298, 1.85 +/- 0.37 ng/mg creatinine; P = 0.7). We conclude that in healthy volunteers the Glu298Asp polymorphism affects endogenous nitric oxide production without affecting nitric oxide-mediated vascular responses. This polymorphism may only have clinical significance in the presence of endothelial dysfunction.