Association between endothelial nitric oxide synthase(ENOS) G894T polymorphism and high altitude(HA) adaptation： a meta-analysis

Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P<0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P<0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.

Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanolinduced liver injury

AIM： To study the expression and activity of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-KB （NF-κB） and tumor necrosis factor-α （TNF-α） expression in the liver. METHODS： Female Sprague-Dawley rats were given fish oil （0.5 mL） along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase （ALT） activity and pathological analysis. Liver malondialdehyde （MDA）, nitric oxide contents, iNOS and eNOS activity were determined. NF-κB p65, iNOS, eNOS and TNF-α protein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction （RT-PCR）. RESULTS： Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration （6 wk） enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, iNOS activity and reduced eNOS activity. NF-κB p65, iNOS and TNF-α protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced iNOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-KB, and TNF-α mRNA expression. CONCLUSION： iNOS expression and activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-KB and TNF-α expression, eNOS activity is reduced, but its mRNA expression is not affected.

Effect of IBD sera on expression of inducible and endothelial nitric oxide synthase in human umbilical vein endothelial cells

AIM： To study the expression of endothelial and inducible nitric oxide synthases （eNOS and iNOS） and their role in inflammatory bowel disease （IBD）. METHODS： We examined the effect of sera obtained from patients with active Crohn＇s disease （CD） and ulcerative colitis （UC） on the function and viability of human umbilical vein endothelial cells （HUVEC）. HUVECs were cultured for 0-48 h in the presence of a medium containing pooled serum of healthy controls, or serum from patients with active CD or UC. Expression of eNOS and iNOS was visualized by immunofluorescence, and quantified by the densitometry of Western blots. Proliferation activity was assessed by computerized image analyses of Ki-67 immunoreactive cells, and also tested in the presence of the NOS inhibitor, 10^-4 mol/L L-NAME. Apoptosis and necrosis was examined by the annexin-V-biotin method and by propidium iodide staining, respectively. RESULTS： In HUVEC immediately after exposure to UC, serum eNOS was markedly induced, reaching a peak at 12 h. In contrast, a decrease in eNOS was observed after incubation with CD sera and the eNOS level was minimal at 20 h compared to control （18%±16% vs 23%± 15% P〈0.01）. UC or CD serum caused a significant increase in iNOS compared to control （UC： 300%±21%; CD： 275% ± 27% vs 108% ± 14%, P〈0.01）. Apoptosis/necrosis characteristics did not differ significantly in either experiment. Increased proliferation activity was detected in the presence of CD serum or after treatment with L-NAME. Cultures showed tube-like formations after 24 h treatment with CD serum. CONCLUSION： IBD sera evoked changes in the ratio of eNOS/iNOS, whereas did not influence the viability of HUVEC. These involved down-regulation of eNOS and up-regulation of iNOS simultaneously, leading to increased proliferation activity and possibly a reduced antiinflammatory protection of endothelial cells.

Correlation of eNOS gene G894T locus polymorphism with the oxidative and inflammatory endothelial function injury in patients with myocardial infarction

Objective:To study the correlation of endothelial nitric oxide synthase (eNOS) gene G894T locus polymorphism with the oxidative and inflammatory endothelial function injury in patients with myocardial infarction.Methods:87 patients with acute myocardial infarction treated in our hospital between May 2012 and December 2015 were selected as acute myocardial infarction (AMI) group and 90 healthy volunteers receiving physical examination during the same period were selected as control group. Peripheral arterial blood was collected to extract genomic DNA and then determine eNOS gene G894T locus polymorphism;peripheral venous blood was collected to separate serum and then determine endothelial injury, oxidative stress and inflammatory reaction indexes.Results:GG genotype proportion and G allele frequency of eNOS gene G894T locus of AMI group were significantly lower than those of control group (P<0.05) while the GT genotype and TT genotype proportion as well as T allele frequency were significantly higher than those of control group (P<0.05);serum nitric oxide (NO), SOD and GSH content of patients with GG genotype were significantly higher than those of patients with GT genotype and TT genotype (P<0.05) while vWF, ET-1, ox-LDL, MDA, -COOH, NF-κB, MCP-1, IL-6 and IL-18 content were significantly lower than those of patients with GT genotype and TT genotype (P<0.05).Conclusions: The proportion of eNOS gene G894T locus G mutation into T significantly increases in patients with myocardial infarction, and G894T locus G mutation into T can aggravate the endothelial injury caused by oxidative stress and inflammation.

Association study of the endothelial nitric oxide synthase gene polymorphisms with essential hypertension in northern Han Chinese

Background Nitric oxide （NO） synthesized by endothelial nitric oxide synthase （eNOS） plays an important role in both the regulation of endothelial function and the control of blood pressure. Up to now, there has been conflicting data regarding the association between three clinically relevant polymorphisms （T-786C, intron4b/a and G894T） of the eNOS gene and essential hypertension.

Association of endothelial nitric oxide synthase polymorphisms with an increased risk of erectile dysfunction

The purpose of our meta-analysis is to examine the associations between three single nucieotide polymorphisms of endothelial nitric oxide synthase （eNOS） gene, G894T, intron 4 and T-786C, and the risk of erectile dysfunction. An electronic database search was performed to identify case-control studies reporting the association between single nucleotide polymorphisms of eNOS gene and erectile dysfunction. Stringent inclusion and exclusion criteria were employed to select high-quality studies for this meta-analysis. Comprehensive Meta-analysis 2.0 software （Biostat Inc., Englewood, New Jersey, USA） was used for statistical analysis of the data extracted from the selected studies. From the initial 203 articles retrieved from database search, this meta-analysis finally selected 12 high-quality case-control studies that conformed to our inclusion criteria. The 12 studies contained a total of 1962 patients with erectile dysfunction and 1752 healthy controls. The results of our meta-analysis showed that G894T correlated with an increased risk erectile dysfunction under both the allele and dominant models （allele： OR = 1.556, 95% CI -- 1.064-2.275, P = 0.023; dominant： OR = 1.613, 95% CI = 1.050-2.476, P = 0.029）. A similar association was found between T-786C and erectile dysfunction under the allele model （OR = 1.679, 95% CI = 1.341-2.102, P 〈 0.001）, but not under the dominant model （all P 〉 0.05）. Our meta-analysis showed that the two single nucleotide polymorphisms in eNOS gene, G894T and T-786C, are strongly associated with the risk of erectile dysfunction.

Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women

Objective： To investigate the relationships between endothelial nitric oxide synthases （eNOS） G894T and 27 bpvariable number tandem repeat （VNTR） gene polymorphisms and osteoporosis in the postmenopausal women of Chinese Han nationality. Methods： In the present study, 281 postmenopausal women from Xi＇an urban area in West China were recruited, and divided into osteoporosis, osteopenia, and normal groups according to the diagnostic criteria of osteoporosis proposed by World Health Organization （WHO）. The bone mineral density （BMD） values of lumbar vertebrae and left hips were determined by QDR-2000 dual energy X-ray absorptiometry. Blood samples were tested for plasma biochemical indicators including testosterone, estradiol, calcitonin, osteocalcin, and procollagen type I amino-terminal propeptide by enzyme-linked immunosorbent assay （ELISA）, tartrate-resistant acid phosphatase by spectrophotometric method, and the content of nitric oxide by Griess method. Genome DNA was extracted from whole blood, and G894T polymorphism of eNOS gene was analyzed by using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method and 27 bp-VNTR polymorphism of eNOS gene was genotyped by PCR method. Then the relationships between genotypes and biochemical indicators, genotypes and osteoporosis, and haplotypes and osteoporosis were analyzed. Results： The average BMD values of the femoral neck, ward＇s triangle and lumbar vertebrae 1-4 （LI-L4） in the subjects with T/T genotype in eNOS G894T locus were significantly higher than those in the subjects with G/T and G/G genotypes （P〈0.05）. The average BMD of the femoral neck in the subjects with a/a genotype of eNOS 27 bp-VNTR locus was evidently higher than that in the subjects with b/b genotype （P〈0.05）. The plasma testosterone and osteocalcin concentrations in the subjects of eNOS G894T G/T genotype were evidently higher than those in the subjects of other genotypes （P〈0.05）; the plasma estradiol concentration in the subjects of eNOS 27 bp-VNTR a/a genotype was obviously higher than that in the subjects of b/b genotype （P〈0.01）. eNOS G/G homozygous frequencies in osteoporosis women, osteopenia women, and normal women were 85.37%, 76.38%, and 83.87%, respectively （P〉0.05）. 0% osteoporosis woman, 0.79% osteopenia women, and 3.23% normal women were eNOS a/a homozygous （P〈0.05）. The frequencies of eNOS 27 bp-VNTR a allele were 5.33% in the osteoporosis group, 10.24% in the osteopenia group, and 16.13% in the normal group （P〈0.05, odds ratio （OR）=0.29, 95% confidence interval （CI）=0.11-0.77）, suggesting that a/a genotype and a allele might have protective effects on osteoporosis. The haplotype analysis showed that G-b was 87.7% （214/244） in the osteoporosis group （P〈0.05, OR=2.48, 95% CI=1. 18-5.18）. G-a was 5.3% （13/244） in the osteoporosis group （P〈0.05, OR=0.29, 95% CI=0. 11-0.77）. G-b was a risk factor for osteoporosis, and G-a a protective factor. Conclusion： eNOS G894T G/T genotype influenced the plasma testosterone and osteocalcin concentrations, and T/T genotype influenced BMD. eNOS 27 bp-VNTR a/a genotype increased plasma estradiol concentration to have a protective effect on osteoporosis.

Assessment of Reversibility in Pulmonary Hypertension Related to Congenital Heart Disease by Using Biomarkers and Clinical Features

Background:Reversibility of pulmonary hypertension(PH)is closely related to the treatment options for and prognosis of children with congenital heart disease.Objective:We combined patient-specific clinical features including diagnosis,age and echocardiographic results,and biomarkers of pulmonary vascular dysfunction to explore the noninvasive methods that can be used to accurately evaluate the reversibility of pulmonary hypertension in congenital heart disease(PH-CHD).Methods:Based on the preoperative systolic pulmonary arterial pressure(sPAP),70 CHD patients were divided into normal,PH-CHD suspected,and confirmed groups.Additionally,biomarkers of circulating endothelial cells(CECs),endothelin-1(ET-1),and endothelial nitric oxide synthase(eNOS)were detected.Patients were categorized into reversible(RPH)and irreversible(IRPH)groups according to the sPAP 6 months after surgery.Risk stratification was performed according to the clinical features and biomarkers.Results:CECs and ET-1 levels in the confirmed group were significantly higher.eNOS was higher in the confirmed and suspected groups than that in the normal group.CECs in the IRPH group were significantly higher compared to the RPH group.No such intergroup differences were observed with respect to ET-1 and eNOS levels.The ROC curve showed that the risk stratification was of high diagnostic value to evaluate reversibility.Conclusion:The CECs,eNOS,and ET-1 were closely related with PH-CHD.CECs and risk stratification have high practical value in assessing the reversibility of PH-CHD.

血清KLF2、NOS3水平对大动脉粥样硬化型急性脑梗死患者的诊断及病情评估价值

[目的]探讨锌指样转录因子2(KLF2)、内皮型一氧化氮合酶3(NOS3)水平在大动脉粥样硬化(LAA)型急性脑梗死(ACI)患者诊断及病情评估中的价值。[方法]将150例LAA型ACI患者根据病情分为轻度组(n=36)、中度组(n=48)和重度组(n=66),另选取同期门诊健康体检者设为对照组(n=150)。比较各组血清KLF2、NOS3水平;ROC曲线分别分析血清KLF2、NOS3水平对LAA型ACI的诊断价值和对发生重度LAA型ACI的预测价值。[结果]LAA型ACI组患者血清KLF2、NOS3水平显著低于对照组(P<0.05)。轻、中、重度组LAA型ACI患者血清KLF2、NOS3水平依次显著降低(P<0.05)。血清KLF2、NOS3二者联合诊断LAA型ACI的AUC为0.858,灵敏度为73.33%,特异度为86.00%,优于KLF2、NOS3各自单独诊断(Z联合检测-KLF2=3.796,Z联合检测-NOS3=4.689,均P<0.001)。血清KLF2、NOS3二者联合预测发生重度LAA型ACI的AUC为0.878,灵敏度为77.27%,特异度为90.48%,优于KLF2、NOS3各自单独预测(Z联合检测-KLF2=2.401,P=0.016;Z联合检测-NOS3=3.070,P=0.002)。[结论]LAA型ACI患者血清KLF2、NOS3水平显著降低,且与病情严重程度显著负相关,二者联合应用对LAA型ACI诊断和病情预测具有较高的评估效能。

基于血清iNOS和eNOS水平建立慢性阻塞性肺疾病急性加重患者机械通气撤机预测模型

目的 基于血清诱导型一氧化氮合酶(iNOS)和内皮型一氧化氮合酶(eNOS)水平建立慢性阻塞性肺疾病急性加重(AECOPD)患者机械通气撤机的预测模型。方法 选择2020年1月至2023年6月在河北北方学院附属第一医院接受机械通气治疗的166例AECOPD患者,按照撤机结局分为撤机成功组(n=112)和撤机失败组(n=54)。比较两组患者的临床资料及入院时、自主呼吸试验(SBT)前的血清iNOS、eNOS水平。采用Logistic回归分析撤机失败的影响因素,采用受试者工作特征(ROC)曲线分析iNOS、eNOS预测撤机失败的价值。结果 与撤机成功组比较,撤机失败组SBT前24 h内的急性生理学与慢性健康状况评价Ⅱ(APACHEⅡ)评分、肌酐(Cr)、iNOS、eNOS水平较高,白蛋白(Alb)水平较低(P<0.05);多因素Logistic回归分析显示,APACHEⅡ、Alb、iNOS、eNOS是撤机失败的影响因素(P<0.05);ROC曲线分析显示,iNOS、eNOS预测撤机失败的ROC曲线下面积为0.648(95%CI 0.563~0.733,P=0.002)、0.755(95%CI 0.683~0.827,P<0.001),以4.418 ng/mL、3.821 ng/mL为最佳截断值,预测敏感度分别为68.52%、83.33%,特异度分别为51.82%、66.36%;iNOS、eNOS与Alb、APACHEⅡ联合预测撤机失败的ROC曲线下面积为0.961(95%CI 0.928~0.993),优于单一指标(Z=7.412、6.682、4.323、4.951,P<0.05),敏感度和特异度分别为94.44%和90.91%。结论 AECOPD患者SBT前血清iNOS、eNOS水平增加与撤机失败相关,SBT前检测iNOS、eNOS联合Alb、APACHEⅡ能够较好地预测撤机结局。

川崎病急性期氧化磷脂和内皮一氧化氮合酶的变化及意义

目的探讨川崎病(Kawasaki disease,KD)急性期患儿的血清氧化磷脂(oxidized phospholipids,OxPLs)和内皮一氧化氮合酶(endothelial nitric oxide synthase,eNOS)水平的变化,分析血清OxPLs和eNOS水平与冠状动脉病变(coronary artery lesion,CAL)的相关性,并探讨其临床意义。方法前瞻性选择95例急性期KD患儿作为KD组,根据是否合并CAL分为CAL亚组和非冠状动脉病变(non-coronary artery lesion,NCAL)亚组;另外选取同期30例仅下呼吸道感染发热患儿作为发热组,30例健康体检儿童作为健康对照组。比较各组一般资料及血清OxPLs、eNOS等实验室指标的差异,分析血清OxPLs和eNOS的相关性。结果KD组OxPLs水平高于发热组及健康对照组(P<0.05),eNOS水平低于发热组及健康对照组(P<0.05)。KD患儿治疗后较治疗前血清OxPLs下降,血清eNOS上升(P<0.05)。CAL亚组血清OxPLs高于NCAL亚组(P<0.05),血清eNOS水平低于NCAL亚组(P<0.05)。KD组患儿OxPLs与eNOS水平呈负相关(rs=-0.353,P<0.05)。结论KD急性期血清OxPLs、eNOS参与了CAL发展,可成为预测KD患儿发生CAL的生物标志物。

海南地区eNOS基因单核苷酸多态性与系统性红斑狼疮的相关性分析

目的探讨海南地区内皮型一氧化氮合酶(eNOS)基因单核苷酸多态性(SNP)与系统性红斑狼疮(SLE)遗传易感性的关系。方法收集2020年1月-2022年12月在海南医学院第一附属医院及海南省人民医院的海南籍SLE患者(SLE组,n=214)及健康对照者(对照组,n=214)的血液样本,通过SNaPshot测序技术检测两组eNOS基因rs3918188、rs1799983及rs1007311位点的碱基情况,并采用logistic回归分析eNOS基因上述3个目的位点的基因型、等位基因及基因模型(显性模型、隐性模型、超显性模型)与SLE遗传易感性之间的相关性。采用HaploView4.2软件分析各位点的单倍体与SLE遗传易感性的关系。结果Logistic回归分析结果显示,rs3918188位点中,CC基因型及C等位基因是SLE遗传易感性的危险因素(CCvs.AA:OR=2.449,P<0.05;Cvs.A:OR=2.133,P<0.001)。在rs3918188位点的隐性模型中,与AA+AC基因型携带者比较,CC基因型携带者的SLE发生风险增高(OR=2.774,P<0.001);而在该位点的超显性模型中,与AA+CC基因型携带者比较,AC基因型携带者的SLE发生风险降低(OR=0.385,P<0.001)。此外,在基因型、等位基因型以及3种基因模型中,rs1799983和rs1007311的多态性均与SLE的易感性无明显相关(P>0.05)。单倍型分析显示,eNOS基因的rs1007311和rs1799983位点之间存在强连锁不平衡,但单倍型与SLE的遗传易感性无明显相关(P>0.05)。结论海南地区eNOS基因rs3918188位点的CC基因型和C等位基因可能是SLE的危险因素,而在超显性模型下该位点AC基因型携带者的SLE发生风险降低。

2型糖尿病患者血清内皮型一氧化氮合酶、网膜素1水平预测糖尿病肾脏疾病发生的价值研究

目的 分析2型糖尿病患者血清内皮型一氧化氮合酶(endothelial nitric oxide synthase,e NOS)、网膜素1(Omentin-1)水平对糖尿病肾脏疾病(diabetic kidney disease,DKD)发生的预测价值。方法 选取2020年5月至2023年2月石家庄市第二医院收治的2型DKD患者124例作为DKD组、单纯2型糖尿病患者125例作为对照组。收集所有患者的临床指标;酶联免疫吸附法检测患者血清eNOS、Omentin-1水平;Pearson法分析DKD患者血清eNOS、Omentin-1和临床指标的相关性;多因素Logistic回归模型分析影响2型糖尿病患者发生DKD的危险因素;受试者工作特征曲线分析2型糖尿病患者血清eNOS、Omentin-1水平对DKD发生的预测价值。结果 与对照组比较,DKD组患者血清总胆固醇[(4.75±0.91)mmol/L比(4.48±0.96)mmol/L]、糖化血红蛋白[(9.32±1.25)%比(8.56±1.23)%]、24 h尿蛋白定量[(2.78±0.31)g比(0.15±0.02)g]、尿微量白蛋白(urinary microalbumin,mAlb)[(273.12±20.41)mg/L比(23.08±3.35)mg/L]、血肌酐(serum creatinine,Scr)[(209.53±22.59)μmol/L比(73.52±9.21)μmol/L]水平显著升高,估算肾小球滤过率(estimatedglomerularfiltrationrate, eGFR)[(72.52±13.51)mL·min^(-1)·(1.73m^(2))^(-1)比(107.34±10.27)m L·min^(-1)·(1.73 m^(2))^(-1)]、血清e NOS[(24.48±3.37)U/L比(33.82±4.52)U/L]、Omentin-1[(28.75±4.42)μg/L比(43.63±6.78)μg/L]水平显著降低(P<0.05);DKD患者血清eNOS与Omentin-1水平呈正相关(r=0.674,P<0.05);血清eNOS、Omentin-1与24 h尿蛋白定量、m Alb、Scr呈负相关(r=-0.456、-0.551、-0.503、-0.527、-0.497、-0.495, P<0.05),与eGFR呈正相关(r=0.523、 0.602,P<0.05);24 h尿蛋白定量、mAlb、Scr是影响2型糖尿病患者发生DKD的危险因素(P<0.05),eGFR、e NOS、Omentin-1是影响2型糖尿病患者发生DKD的保护因素(P<0.05);血清eNOS、Omentin-1两者联合预测2型糖尿病患者发生DKD的曲线下面积(area under curve,AUC)为0.942,分别高于血清e NOS(AUC=0.882)、Omentin-1(AUC=0.862)各自单独预测2型糖尿病患者发生DKD的AUC(P<0.05)。结论 DKD患者血清eNOS与Omentin-1水平均呈低表达,二者联合检测对2型糖尿病患者发生DKD有一定预测价值。

病毒性脑炎患儿脑脊液和血清中SIL-2R、eNOS、CD93水平与疾病进展及预后的关系

目的探究病毒性脑炎(viral encephalitis,VE)患儿脑脊液和血清中可溶性白细胞介素-2受体(soluble interleukin-2 receptor,SIL-2R)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、白细胞分化抗原93(cluster of differentiation 93,CD93)水平与疾病进展及预后的关系。方法前瞻性选取2021年1月—2024年1月收治的VE患儿102例作为VE组,根据疾病进展分为轻症亚组(64例)和重症亚组(38例),根据预后情况分为预后良好亚组(29例)和预后不良亚组(73例);另选取同期经检查排除VE的其他中枢神经系统疾病患儿102例作为对照组。分析VE患儿预后不良的影响因素,以及脑脊液和血清中SIL-2R、eNOS、CD93对VE患儿预后不良的预测价值。结果VE组、重症亚组、预后不良亚组脑脊液和血清SIL-2R、eNOS、CD93水平均显著升高(P<0.05)。多因素logistic回归分析显示,脑脊液和血清SIL-2R、eNOS、CD93水平高为VE患儿预后不良的危险因素(P<0.05)。受试者操作特征曲线分析显示,脑脊液SIL-2R、eNOS、CD93三者联合预测VE患儿预后不良的价值优于各指标单独预测(P<0.05);血清SIL-2R、eNOS、CD93三者联合预测VE患儿预后不良的价值优于各指标单独预测(P<0.05)。结论VE患儿脑脊液和血清中SIL-2R、eNOS、CD93水平均显著升高,且与疾病进展及预后有关。

内皮系统基因及多态性与高血压的相关性研究进展

高血压是常见的慢性病,是以动脉血压持续升高为特征的心血管综合征,是我国心脑血管病死亡的重要原因。目前高血压已成为一个严峻的公共卫生问题。高血压发病机制复杂多样,随着对发病机制的不断探索,发现遗传因素在高血压的发生发展中起着重要作用。其中内皮系统基因及其动态性在高血压中发挥的作用已逐渐成为研究热点。现就几个内皮系统基因及其多态性与高血压的关系展开论述,以期为临床高血压的诊断和治疗提供新的思路。

AGT-M235T及eNOS-T786C基因多态性与急性心肌梗死的相关研究

目的探讨血管紧张素原(AGT)-M235T、内皮型一氧化氮合酶(eNOS)-T786C基因多态性与急性心肌梗死(AMI)的相关性。方法选取2021年7月至2023年7月在玉林市中医医院就诊的AMI患者200例作为AMI组,同期体检健康者200名作为对照组,比较两组的基因型及等位基因频数的差异。结果AMI组男女间的eNOS-T786C基因型及等位基因频数比较,差异有统计学意义(P<0.05);对照组男女间的AGTM235T基因型、AGT-M235T等位基因及eNOS-T786C基因型频数比较,差异有统计学意义(P<0.05)。两组女性的eNOS-T786C基因型及等位基因频数比较,差异有统计学意义(P<0.05)。分别以GG和TT基因型作为参照进行二元logistic回归分析,结果表明AA及CC基因型可能是AMI患病的危险因素(AA:OR=2.281,P<0.05;CC:OR=2.934,P<0.05),而GA基因型可能是AMI患病的保护因素(OR=0.803,P<0.05)。结论AGT-M235T的AA基因型及eNOS-T786C的CC基因型与AMI易感性密切相关,临床需要重视AMI患者相关基因型的危险因素及保护因素。

汉族人群NOS3 A-922G、NOS3 T-786C与NOS3 G894T SNP的等位基因及其组合分布与高血压的相关性

为了分析汉族人群一氧化氮合酶基因NOS3 A-922G、NOS3 T-786C与NOS3 G894T单核苷酸多态性(singlenuc leotide polymorph ism,SNP)的等位基因及其组合分布与高血压病的相关性,选取无亲缘关系的高血压病人192例(男97例,女95例)以及无亲缘关系的健康个体122例(男76例,女46例)为对照组,提取静脉血白细胞基因组DNA,采用等位基因特异性引物PCR技术检测NOS3 A-922G、NOS3 T-786C与NOS3 G894T 3个位点的基因型。其结果显示:高血压病组与对照组NOS3 G894T、NOS3A-922G及NOS3 T-786C各等位基因型及其基因单倍型频率比较无显著性差异(P>0.05)。男、女性别分层研究:无论男亚组还是女亚组均未发现NOS3 A-922G、NOS3 T-786C与NOS3 G894T各个位点SNP与高血压病有相关性。等位基因组合分布研究发现NOS3 G894G+A-922G+T-786T组合基因型总体频率分布在高血压病组与正常对照组之间有显著性差异(P<0.05,χ2=4.5944)。男、女性别分层研究:男亚组上述3个位点SNP的各个组合基因型分布频率在高血压病组与正常对照组之间无显著性差异(P>0.05);女亚组中携带NOS3 G894G+A-922G+T-786C的组合基因型分布频率在高血压病组与正常对照组之间有显著性差异(P<0.01,χ2=8.502)。研究发现,在中国汉族人群中NOS3A-922 G、NOS3 T-786C与NOS3 G894T SNP与高血压病无明确的相关性,且无性别差异。组合分布研究发现,NOS3 G894G+A-922G+T-786C的组合基因型分布频率在高血压病女性亚组较健康女性亚组明显减低,提示携带该组合基因型女性人群可能不易患高血压病。

中国人eNOS基因VNTR多态性的基因型与等位基因频率(英文)

一氧化氮合酶 (nitricoxidesynthase ,NOS)催化L 精氨酸的氧化反应生成L 瓜氨酸和一氧化氮 (nitricoxide,NO)。NO可通过cGMP依赖的信号传导途径介导平滑肌细胞舒张 ,是调节血管张力的重要信使分子。NO尚可抑制血小板凝集 ,对血栓形成起重要调节作用。目前在哺乳动物中已发现细胞来源、表达方式和活性调节不同的 3种NOS同工酶 ,分别为神经元型NOS(neuronalNOS ,nNOS)、诱导型NOS(inducibleNOS ,iNOS)和内皮细胞型NOS(endothelialNOS ,eNOS)。人的eNOS基因位于第 7号染色体长臂 (7q36) ,全长约 2 1kb ,含有 2 6个外显子和 2 5个内含子。eNOS基因存在多个与心脑血管疾病相关的基因多态性位点。其中位于第 4内含子的一个以 2 7bp为核心的数目可变性串联重复序列(variablenumberoftandemrepeat,VNTR)多态性位点 ,已被证实与原发性高血压、心肌梗死和静脉血栓形成有关。目前在我国尚缺乏NOS基因多态性在正常人群中基因型及等位基因频率分布的统计资料。为此 ,我们从 31 6名健康中国人的基因组DNA检测了eNOS基因第 4内含子VNTR多态性的基因型和等位基因 ,鉴定出重复 6次、5次和 4次的 3种等位基因 ,以及 6/ 5杂合、5/ 5纯合、5/ 4杂合和 4 / 4纯合的 4种基因型。同时我们将正常中国人eNOS基因VNTR多态性的基因?

内皮型一氧化氮合酶基因第4内含子基因多态与福建汉族脑血管病的相关性

目的研究福建汉族人内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)基因第4内含子27 bp可变串联重复序列(variable number of tandem repeat,VNTR)与脑血管病关系。方法依据缺血性卒中TOAST(Trial of ORG 10172 in Acute Stroke Treatment)分型收集132例大动脉粥样硬化性卒中(large arteryatherosclerosis,LAA),63例腔隙性脑梗死(lacunar infarction,LI)及62例高血压性脑出血患者为病例组,同时选择年龄、性别匹配的237名健康者为对照组,采用聚合酶链反应结合2%琼脂糖电泳技术检测eNOS基因第4号内含子27 bp VNTR的多态性。结果正常福建汉族人eNOS基因第4内含子除bb,ab,aa基因型外,尚出现罕见的bc基因型,其基因型频率分别为0.789,0.203,0.004,0.004;b、a、c等位基因频率分别为.892,0.106及0.002。LAA及LI患者27 bp VNTR多态与对照组差别无统计学意义,LAA组bc基因型频率(0.030)虽明显高于对照组(0.004),但差异无统计学意义;缺血性卒中伴/不伴高血压病与该基因多态无相关性。高血压性脑出血患者的aa基因型频率为0.048,明显高于bb+ab基因型(OR=11.42,95%CI:1.209-117.892,P<0.05)。结论eNOS第4内含子aa基因型可能是福建汉族人高血压性脑出血的遗传危险因素,但该位点多态性与福建汉族LAA及LI无相关性。

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。