NAD(P)H氧化酶p22phox亚基C242T基因多态性与脑梗死的关系

目的了解上海地区汉族脑梗死患者烟酰胺腺嘌呤二核苷酸磷酸氧化酶[NAD(P)H氧化酶]p22phox亚基C242T基因多态性和等位基因频率的分布情况,探讨其多态性与脑梗死的关系。方法采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP),对176例脑梗死患者和131名健康老年人的C242T位点进行基因分型,计算等位基因的频率分布。结果脑梗死患者血清三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血糖浓度和血压与老年健康对照组之间差异具有统计学意义(P<0.05)。脑梗死组与老年健康对照组的CC、CT、TT基因型频率分别为92.05%、7.95%、0与93.89%、5.34%、0.76%;C、T等位基因频率分别为96.02%、3.98%与96.56%、3.44%,2组间的差异均无统计学意义(P>0.05)。结论 p22phox亚基C242T位点的单核苷酸多态性与脑梗死的发生可能无关。     

NAD（P）H氧化酶及其基因多态性对心脑血管疾病的作用

烟酰胺腺嘌呤二核苷酸磷酸（NAD（P）H）是人体中重要的生物分子,而NAD（P）H氧化酶催化NAD（P）H的反应产物为超氧阴离子（superoxideanion,·O2^-）,后者在维持机体免疫、代谢、血管生理功能等诸多方面都具有关键作用。NAD（P）H氧化酶基因多态性的发生可影响到酶生物活性功能,进而引发机体相应生理、病理反应的改变。     

NADPH氧化酶p22phox亚基C242T基因多态性与糖尿病患者颈总动脉粥样硬化相关性研究

目的：研究2型糖尿病（T2DM）患者NADPH氧化酶p22phox亚基242位点基因多态性分布,探讨该基因多态性与糖尿病患者颈总动脉粥样硬化的相关性。方法：将273例T2DM患者分为颈总动脉内-中膜（IMT）正常、增厚、无斑块与有斑块4组,应用聚合酶链反应-限制性片段长度多态性技术对他们的NADPH氧化酶p22phox亚基242位点进行基因型分析。结果：NADPH氧化酶p22phox亚基242位点基因多态性在IMT正常和IMT增厚的T2DM患者中的分布存在显著性差异（P<0.05）;在无斑块和有斑块的T2DM的患者中,NADPH氧化酶p22phox亚基242位点基因多态性亦存在显著性差异（P<0.05）。结论：NADPH氧化酶p22phox亚基242位点（C-T）基因多态性与T2DM患者颈总动脉IMT的增厚、斑块的发生存在相关性。     

帕拿森病遗传易患性与依赖还原型辅酶Ⅰ／Ⅱ醌氧化还原酶基因多态性的关系

背景：帕金森病的病因至今尚未阐明，遗传易患性学说是目前解释帕金森病的主要理论，但哪些遗传因素与此有关，还没有定论。目的：探讨依赖还原型辅酶Ⅰ／Ⅱ醌氧化还原酶基因cDNA609位碱基C→T点突变所致的基因多态性与帕金森病遗传易患性的关系。设计：以患者和健康人为研究对象，非随饥同期化对照研究。单位：两所大学医院的神经内科和一所大学医院的老年病研究所。对象：1994—09／1997—09中山大学第一附属医院神经科门诊诊断为帕金森患者126例(帕金森病组)，年龄46～73岁．其中男74例，女52例；136名健康成人(对照组)，其中男66名，女70名，同期来自门诊健康查体，年龄40～72岁。方法：采用聚合酶链反应限制性片段长度多态性(PCR—RFLP)的方法分析帕金森病人组与健康成人对照组NQO1基因多态性。主要观察指标：NQO1基因cDNA609位碱基C→T点突变的频率及其基因型。结果：帕金森病组的T等位基因频率为52％，而对照组为43％，两组差异有显著意义(P&;lt;0．05)；基因型分布在帕金森病和对照组之间差异有显著意义(P&;lt;0．05)，带T等位基因的个体患帕金森病的风险增加3．8倍。结论：NQ01基因cDNA609突变T等位基因可能是帕金森病发生的危险性因素，与帕金森病的遗传易患性有关。     

脑梗死与基因多态性

目的：脑梗死是多因素共同作用的复杂的多基因遗传病，探讨脑梗死与基因多态性问的相关性。资料来源：应用计算机检索PubMed1 980—01／2005-03与脑梗死基因多态性相关文章，检索词“cerebral infarction，gene polymophysm”并限定文章语种为English。检索维普中文科技期刊全文数据库1989—01／2005-03期间的相关文章，并限定文章语种为中文，检索词“脑梗死，基因多态性”。资料选择：对资料进行初审，选取试验包含上述关键词的文献，然后开始查找全文。纳入标准：①临床试验，无论是否为单盲，双盲或非盲法。②试验包含正常对照组和脑梗死组。排除综述文献和Meta分析。资料提炼：共收集到符合主题的英文研究性文献65篇，其中55篇文献符合纳入标准；收集到中文文献113篇，28篇文献符合纳入标准。选择有代表性的19篇中、英文文献列入参考文献。资料综合：研究发现血管紧张索Ⅱ受体、血管紧张素转换酶、载脂蛋白E、纤维蛋白原、雌激素受体、纤溶酶原激活物抑制剂1的基因多态性与脑梗死相关。结论：脑梗死的发病和预后与多种因素有关，尽管基因多态性与脑梗死的相关性研究成果不尽一致，但对各种相关基因多态性的研究为脑梗死的防治提供了新的思路。     

脂蛋白（a）、载脂蛋白（B）基因多态性与心肌梗死的相关性研究

目的了解脂蛋白 (a)、载脂蛋 B基因多态性与心肌梗死的关系。方法用免疫透射比浊法测定血清脂蛋白 (a)。采用聚合酶链反应 /限制性酶切法 (PCR) /RFL P)分析 Apo B基因。结果正常健康人组脂蛋白 (a) (170±148) m g/L ,Apo BX 等位基因频率为 0 .0 82 ;高血压组脂蛋白 (a) (4 82± 15 1) mg/L ,Apo BX 等位基因为 0 .0 30 ;心肌梗死组脂蛋白 (a) (781± 2 78) mg/L ,Apo BX 等位基因频率为 0 .30 2。结论脂蛋白 (a)的水平 (≥ 30 0 0 m g/L ) ,Apo BX 等位基因频率与心肌梗死高度相关 ,高血压组的脂蛋白 (a)、Apo BX 等位基因频率与正常健康人相比较无明显差异。     

载脂蛋白H基因启动子32位点多态性与脑梗死的相关性研究

目的：研究上海地区汉族人的载脂蛋白H（ApoH）启动子32位点多态性和等位基因的分布情况,并探讨其在脑梗死（CI）患者和对照人群中的分布特点．以及其与脑梗死间的相关性。方法：采集278例CI患者及195名老年对照者的血液样本．以提取的基因组DNA为模版．应用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）技术检测Aport启动子32位点基因多态性．并用基因测序方法验证PCR-RFLP结果。结果：ApoH启动子32位点基因多态性主要以CC和CA基因型存在。CI患者与对照者间Aport启动子32位点的等位基因频率、基因型频率分布差异无统计学意义（P〉0．05）,但CI患者与对照者间的三酰甘油、总胆固醇、低密度脂蛋白胆固醇（LDL-C）及血糖水平有统计学差异（P〈O．05）。此外,仅在女性CI患者中观察到。CC与CA基因型携带者间的LDL—C水平有统计学差异（P〈0．05）。结论：Aport启动子32位点基因多态性可能与CI易感性无关．但与血脂代谢有一定关联。     

白细胞介素基因多态性与脑梗死的关系

脑梗死是由多种原因引起脑血管供血障碍,导致局部脑组织因缺血、缺氧而出现坏死或软化等病理性改变的疾病。目前认为,其是由多因素共同作用的复杂多基因遗传病,高脂血症、高血压、动脉粥样硬化、吸烟等均是主要的危险因素。近年来,又有许多研究者致力于脑梗死与基因多态性相关性的探索。     

白细胞介素10-819C／T、-1082G／A基因多态性与脑梗死的关系

目的探讨白细胞介素10（IL-10）基因多态性与脑梗死（CI）的关系。方法采用突变错配扩增技术,结合血液生化和血压等临床资料,对189例急性CI患者（CI组）和92例非急性CI者（对照组）的IL-10启动子1082G／A和819C／T基因的单核苷酸多态性（SNP）位点与CI的关系进行研究。结果IL-10启动子1082G／A和819C／T的CI组的基因型和等位基因频率分布与对照组相比差异均无统计学意义（P〉0．05）;CI组的IL-10启动子1082AA型的收缩压明显高于（AG＋GG）型（P〈0．05）,且AA型的收缩压、舒张压、血糖均明显高于对照组（P〈0．05）,（AG＋GG）型的高密度脂蛋白胆固醇（HDL—C）明显低于对照组（P〈0．05）;CI组的IL-10启动子819CC型的收缩压、舒张压均明显高于TT型和CT型（P〈0．05）,且TT型的收缩压、舒张压、血糖均明显高于对照组（P〈0．05）,CT型的HDL—C明显低于对照组（P〈0．05）,CC型的收缩压、舒张压明显高于对照组（P〈0．05）。结论IL．10基因启动子1082G／A和819C／T的多态性与CI发生无明显相关,但与CI的发展和预后有-定关联。     

NAD(P)H oxidase p22phox Gene C242T polymorphism and lipoprotein oxidation

BACKGROUND: Vascular NAD(P)H oxidase is a key enzyme of superoxide anion production in human vessel walls. The C242T mutation in the CYBA gene coding for p22phox, a component of the enzyme, may change the redox state. The aim of this study was to evaluate the influence of the polymorphism on serum concentrations of oxidative stress markers. METHODS: Serum samples were collected from 134 Type 2 diabetic patients and analyzed for oxidized high-density lipoprotein (HDL) by in-house ELISA, and oxidized low-density lipoprotein (LDL) and thiobarbituric acid reactive substance (TBARS) by commercial kits. For genotyping, the Taqman PCR method was adapted to detect the polymorphism. RESULTS: Circulating concentrations of oxidized HDL were about 1.5-fold lower in those of the CT/TT genotypes than the CC genotype [3.3 +/- 0.3 and 5.0 +/- 0.3 U/dl (mean +/- S.E.M.), respectively; multiple regression analysis, p=0.006], whereas concentrations of oxidized LDL were slightly greater (1.1-fold, p=0.01) in those with the CT/TT genotypes. However, no significant difference was observed in TBARS between the genotypes. CONCLUSIONS: The effect was inconsistent among the markers, but these results suggest that the CYBA C242T polymorphism is involved in NAD(P)H oxidase activity and affects oxidation of lipoproteins by altering the redox state in the vasculature.     

Investigation of the C242T polymorphism of NAD(P)H oxidase p22 phox gene and ischaemic heart disease using family-based association methods

Ischaemic heart disease is a complex phenotype arising from the interaction of genetic and environmental factors. Excessive production of reactive oxygen species leading to endothelial dysfunction is believed to be important in the pathogenesis of ischaemic heart disease. The NAD(P)H oxidase system generates superoxide anions in vascular cells; however, the role of the C242T polymorphism of the NAD(P)H oxidase p22 phox gene in ischaemic heart disease is unclear due to contradictory results from case-control studies. Consequently, we applied family-based association tests to investigate the role of this polymorphism in ischaemic heart disease in a well-defined Irish population. A total of 1023 individuals from 388 families (discordant sibships and parent/child trios) were recruited. Linkage disequilibrium between the polymorphism and ischaemic heart disease was tested using the combined transmission disequilibrium test (TDT)/sib-TDT (cTDT) and pedigree disequilibrium test (PDT). Both cTDT and PDT analyses found no statistically significant excess transmission of either allele to affected individuals (P =0.30 and P =0.28, respectively). Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the C242T polymorphism of the p22 phox gene has a significant role in the development of ischaemic heart disease in our population.     

NADH/NADPH oxidase p22phox C242T polymorphism and coronary artery disease in the Australian population

BACKGROUND: Oxidative stress induced by the superoxide anion (.O2-) has been implicated in atherogenesis. The NADH/NADPH oxidase system is involved in.O2- production and p22 phox is an essential component of that system. MATERIAL AND METHODS: We analysed the p22 phox C242T polymorphism in 689 consecutive Australian Caucasians aged 相似文献   

对氧磷酶基因多态性与脑梗死关联性的探讨

目的:探讨我国上海地区汉族人群的对氧磷酶1(PON1)基因T-107C、PON2 Ser311Cys基因多态性与脑梗死发病乃至颈动脉硬化之间的关系。方法:采用聚合酶链反应-限制性片段长度多态性技术,检测134例脑梗死患者和103名健康对照者PON1 T-107C、PON2 Ser311Cys的多态性基因型,并研究其对脑梗死发病的影响。结果:多因素多元逐步Logistic回归分析显示,三酰甘油、总胆固醇是脑梗死的独立危险因素;同时,脑梗死组的PON1 T-107C、PON2 Ser311Cys基因型及等位基因频率分布与健康对照组间差异均有统计学意义(P     

Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants

Several risk factors for coronary artery disease (CAD) induce atherosclerosis through endothelial activation and dysfunction, and ample evidence now suggests that the balance between production and removal of reactive oxygen species (ROS) - a condition termed oxidative stress - is implicated in such processes. A main source of ROS in vascular cells is the reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase system. This is a membrane-associated enzyme, composed of five subunits, catalyzing the one-electron reduction of oxygen, using NADH or NADPH as the electron donor. One of the system subunits, termed p22-phox, has a polymorphic site on exon 4, associated with variable enzyme activity. This polymorphism is generated by a point mutation (C(242)T) producing a substitution of histidine with tyrosine at position 72, which affects one of the heme binding sites essential for the NAD(P)H enzyme activity. The consequent decrease of superoxide production thus characterizes a phenotype candidate for conferring to the carrier a reduced susceptibility to CAD. At present, however, the body of evidence from current literature is not yet sufficient to confirm or exclude the hypothesis that the C(242)T polymorphism protects from CAD. The functional effects of this polymorphism and the potential and its pathophysiological consequences also need further investigation.     

NADH/NADPH oxidase p22 phox C242T polymorphism and lipid peroxidation in coronary artery disease

The nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is a major source of superoxide anion (^·O₂^–) production in the human vasculature and may therefore influence lipid peroxidation and severity of atherosclerosis. This study aimed to investigate a hypothetical influence of the p22 phox C242T polymorphism on the generation of malondialdehyde (MDA), extent and clinical onset of coronary artery disease (CAD) in patients. We studied 108 male Caucasians with angiographically documented CAD and 45 controls free of vascular disease under 60 years of age. p22 phox C242T genotypes and MDA levels were determined. Additional information was obtained from each subject on classic risk factors and clinical events of CAD. Genotype distribution in CAD‐patients and controls was thymine–thymine (TT): 13·8% (13·3%), cytosine–thymine (CT): 46·3% (53·3%) and cytosine–cytosine (CC): 39·8% (33·3%), respectively. No significant influence was seen of the p22 phox C242T polymorphism on corresponding mean MDA levels in both groups. Furthermore, age at onset of first time angina pectoris (AP) and myocardial infarction (MCI) was not significantly different between genotype groups. It is concluded that the C242T polymorphism of the p22 phox gene is not associated with lipid peroxidation as measured by MDA, and is not a genetic risk marker for CAD Caucasians.