对氧磷酶基因192位点多态性与动脉粥样硬化性脑梗死的关系

目的:研究动脉粥样硬化性脑梗死与血清对氧磷酶(PON1)基因192位点多态性的关系。方法:应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法,对52例动脉粥样硬化性脑梗死患者,48例正常人的PON1基因192位点多态性进行分析,同时检测血脂水平。结果:脑梗死组及正常组均以QR基因型为主,频率分别为0.50,0.54,QQ,RR基因型频率分别为0.10、0.25,0.40、0.21,两组人群基因型分布处于Hardy-Weinberg平衡。脑梗死组R等位基因频率明显高于正常组,分别为0.65,0.48(χ2=4.18P<0.05)。且脑梗死组血清胆固醇、三酰甘油、载脂蛋白B水平高于正常组,低密度脂蛋白胆固醇有升高趋势,而高密度脂蛋白胆固醇、载脂蛋白A1低于正常组。结论:PON1基因192位点多态性可能与动脉粥样硬化性脑梗死有关。R等位基因可能为动脉粥样硬化性脑梗死的相对危险因素。且血脂异常参与脑梗死的发病。     

对氧磷酶基因192位点多态性与动脉粥样硬化性脑梗死的关系

目的：研究动脉粥样硬化性脑梗死与血清对氧磷酶(PON1)基因192位点多态性的关系。方法：应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法，对52例动脉粥样硬化性脑梗死患者，48例正常人的PON1基因192位点多态性进行分析，同时检测血脂水平。结果：脑梗死组及正常组均以QR基因型为主，频率分别为O.50，O.54，QQ,RR基因型频率分别为O．10、O．25，O.40、O.21，两组人群基因型分布处于Hardy-Weinberg平衡。脑梗死组R等位基因频率明显高于正常组，分别为O.65，O.48(χ^2=4.18 P&;lt;O.05)。且脑梗死组血清胆固醇、三酰甘油、载脂蛋白B水平高于正常组，低密度脂蛋白胆固醇有升高趋势，而高密度脂蛋白胆固醇、载脂蛋白A1低于正常组。结论：PON1基因192位点多态性可能与动脉粥样硬化性脑梗死有关。R等位基因可能为动脉粥样硬化性脑梗死的相对危险因素。且血脂异常参与脑梗死的发病。     

动脉粥样硬化候选基因屏氧酶1基因192位Gln-Arg多态性对血脂的影响

目的:探讨屏氧酶1基因192位Gln-Arg多态性与血脂水平的关系。方法:从社区正常人群、健康体检者和患者中抽取1019例受试者,其中680例脑卒中患者及339例正常对照组人群,男606例,女413例。采用聚合酶链式反应-限制性片段长度多态性方法测定屏氧酶1基因多态性。结果:非心脑血管病、脑出血、脑梗死患者年龄、性别、体质量指数、总胆固醇和低密度脂蛋白胆固醇比较,差异无显著性意义(P>0.05),三者血清空腹血糖、三酰甘油、低密度脂蛋白胆固醇比较,差异有显著性意义(P<0.05)。屏氧酶13种基因型(QQ,QR,RR基因型)各血脂水平差异无显著性意义(P>0.05),其中QQ基因型的三酰甘油、胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平分别为(1.58±0.89),(4.82±1.01),(1.39±0.38)和(2.84±0.75)mmol/L;QR基因型分别为(1.59±0.99),(4.78±1.00),(1.36±0.38)和(2.82±0.80)mmol/L;RR基因型分别为(1.57±0.87),(4.84±1.05),(1.34±0.39)和(2.87±0.87)mmol/L。同一性别不同基因型之间各血脂水平差异无显著性意义(P>0.05)。男女两性屏氧酶1各基因型的比例相近(P>0.05)。男女不同性别之间屏氧酶1基因各基因型的血脂水平存在差异,尤其以高密度脂蛋白胆固醇明显(P<0.05)。结论:屏氧酶1基因192位Gln-Arg各基因型间血脂水     

脑源性神经营养因子基因多态性与散发性帕金森病的相关性

背景：脑源性神经营养因子对多巴胺能神经元具有特殊保护作用，而帕金森病的主要病理改变是黑质致密部多巴胺能神经元的变性和丢失。帕金森病的发生可能与脑源性神经营养因子基因多态性有关。目的：探讨中国人群中脑源性神经营养因子基因多态性与散发性帕金森病的相关性，以期为该病的一级康复预防提供遗传学数据。设计：以散发性帕金森病患者DNA为研究对象，以社区健康人群DNA为对照，探索性基础研究。单位：华中科技大学同济医学院附属协和医院神经内科，华中科技大学人类基因组中心。对象：以武汉协和医院神经内科提供85例散发性帕金森病患者(研究组，均为汉族，居在华中地区长期居住)DNA和华中科技大学人类基因组中心提供的健康人(对照组，均为汉族，居在华中地区长期居住)DNA为研究对象。方法：采用聚合酶链反应一限制性片段长度多态性分析方法，对健康人和散发性帕金森病患者进行基因分型。主要观察指标：检测两组G196A和C270T多态性位点的基因型及等位基因。结果：研究组和对照组G196A多态性位点均以G／A基因型为主，频率分别为50．6％和52．0％；C270T多态性位点均为C／C基因型。两组间脑源性神经营养因子基因G196A和C270T多态性位点各基因型和等位基因频率差异均无显著性(P&;gt;0．05)。结论：中国华中地区汉族人群中脑源性神经营养因子基因多态性与散发性帕金森病发病无明显关系。     

对氧磷酶1基因Q192R和L55M位点多态性与川崎病冠状动脉损伤的相关性

目的探讨对氧磷酶1(paraoxonase 1, PON1)基因Q192R和L55M位点基因多态性与川崎病患儿冠状动脉损伤的关系。方法川崎病患儿73例(川崎病组),其中有冠状动脉损伤34例为损伤组,无冠状动脉损伤39例为未损伤组;同期50例健康儿童为对照组。3组采集空腹静脉血提取全血DNA,采用限制性片段长度多态性PCR技术检测PON1基因Q192R和L55M位点多态性,并进行比较。结果川崎病组Q192R位点RR、QR基因型分布频率(40.0%、44.0%)及Q等位基因频率(38.0%)与对照组(39.7%、45.2%、37.7%)比较差异无统计学意义(P0.05),L55M位点LL基因型分布频率及L等位基因频率(90.0%、95.0%)与对照组(86.3%、92.5%)比较差异无统计学意义(P0.05)。损伤组PON1基因Q192R位点RR基因型分布频率(52.9%)及R等位基因频率(72.1%)均高于未损伤组(28.2%、53.8%)(P0.05)。损伤组PON1基因L55M位点LM+MM基因型分布频率(23.5%)及M等位基因频率(13.2%)均高于未损伤组(5.1%、2.6%)(P0.05)。结论 PON1基因Q192R和L55M位点基因多态性与川崎病发生无明显相关性,与川崎病患儿冠状动脉损伤关系密切。     

肝脂酶基因-763A/G多态性与高三酰甘油血症的关系

目的:探讨汉族人群肝脂酶(HL)基因启动子763A/G多态性与血脂的关系。方法:运用聚合酶链反应-限制性内切酶片段长度多态性技术,对112名三酰甘油(TG)正常者和103例高三酰甘油症(HTG)患者的HL基因启动子763A/G多态性进行研究。结果:HL启动子763G等位基因频率在HTG组(0.4466)与TG正常组(0.4063)间差异无显著性(P>0.05)。除HTG男性组的基因型频率明显高于TG正常男性组(P0.05)。在HTG组中显示AG+GG型的低密度脂蛋白胆固醇(LDL-C)水平明显高于AA型(P<0.05);而在TG正常组中可见AG+GG型的载脂蛋白A1(ApoA1)浓度高于AA型(P<0.05)。HTG女性组AG+GG型LDL-C和ApoA1水平明显高于同组AA型(P<0.05),各项血脂水平与TG正常组相同基因型间均有明显差异(P<0.05)。另见在HTG组中除男性组AA型的高密度脂蛋白胆固醇(HDL-C)、LDL-C和ApoA1水平与TG正常组同基因型血脂无差异外,其他各项血脂均有显著差异(P     

肝脂酶基因启动子250G/A多态性与冠心病的关系

目的探讨本地区汉族人肝脂酶(HL)基因启动子250G/A多态性与冠心病的关系。方法采用聚合酶链反应限制性片段长度多态性(PCR-RELP)技术检测了103例冠心病患者和69名健康对照组汉族人HL启动子250G/A多态性基因型,探讨了其对血脂、载脂蛋白水平的影响。结果冠心病组的基因型和等位基因频率分布与正常老年组之间的差异无统计学意义;冠心病组的高密度脂蛋白胆固醇(HDL-C)载脂蛋白A1(apoA1)水平与正常老年组同基因型之间的差异具有统计学意义(P<0.05);冠心病组的apoA1水平(1.20±0.31)g/L明显低于正常老年组的同基因型(1.49±0.23)g/L;冠心病组的HDL-C水平(1.30±0.31)mmol/L明显高于同组的无突变型(1.16±0.32)mmol/L。经多元Logistic逐步回归分析的显示,TG是冠心病危险因子,apoA1是保护因子(P<0.05),但未见A等位基因是一个危险因子。结论在冠心病患者中,HL启动子250G/A基因多态性对血脂水平有一定影响。     

IL-17基因多态性与支气管哮喘患儿血清TIgE、ECP的关系分析

目的分析白细胞介素(IL)-17基因多态性与支气管哮喘患儿血清总IgE(TIgE)、嗜酸性粒细胞阳离子蛋白(ECP)的关系。方法将该院2018年1—12月收治的60例哮喘患儿设为哮喘组,同期于该院行健康体检的60例健康儿童设为对照组,采用PCR-限制性片段长度多态性分析法检测2组IL-17基因多态性,采用免疫比浊法、酶联免疫吸附试验法分别检测其血清TIgE、ECP水平,比较2组IL-17基因多态性、TIgE和ECP水平及不同基因型、不同等位基因型患儿血清TIgE、ECP水平。结果哮喘组中IL-17A-152G/A位点中AA型基因频数频率、A等位基因频数频率,IL-17F 7488T/C位点中TT型基因频数频率、T等位基因频数频率,血清TIgE、ECP水平均显著高于对照组(P<0.05)。哮喘组IL-17A-152G/A位点AA型基因血清TIgE显著高于AG、GG型(P<0.05)。IL-17A-152G/A位点A等位基因携带患儿血清TIgE显著高于非A等位基因携带患儿(P<0.05)。哮喘组IL-17F 7488T/C位点不同基因型、等位基因携带者间血清TIgE、ECP与对照组比较,差异无统计学意义(P>0.05)。结论IL-17A-152G/A基因多态性与哮喘易感性有关,变异等位基因A携带患儿哮喘风险更高,尤其是突变纯合子AA基因型,野生型TT纯合子与哮喘也有一定关联性;且IL-17基因多态性虽与血清ECP均无明显关联,但血清ECP在哮喘患儿中仍明显高表达。     

载脂蛋白B基因EcoRI、XbaI、MspI及载脂蛋白AI基因-75bp、+83bp位点多态性与哈萨克族血脂异常的关系

目的:分析载脂蛋白B(apoB)基因EcoRI、XbaI、MspI位点和载脂蛋白AI(apoAI)基因-75bp、+83bp位点多态性与哈萨克族(哈族)人血脂异常的关系。方法:采用聚合酶链式反应-限制性片段长度多态性分析法检测275例哈族血脂异常患者(血脂异常组)和252例哈族血脂正常对照者(对照组)的apoB基因EcoRI、XbaI、MspI位点和apoAI基因-75bp、+83bp位点多态性。检测甘油三酯、血浆总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、apoB、apoAI的水平。结果:(1)各个位点各基因型及等位基因频率在两组之间差异无显著性。(2)血脂异常组和对照组各基因型联合的总体分布不同(χ2=19.26,P<0.05)。E+-/X--/Ms++/M1/M2(联合10)的比率在血脂异常组(45/275)显著高于对照组(22/+-++252,χ2=5.37,P<0.05)。E++/X+-/Ms+-/M1/M2(联合11)的比率在血脂异常组(30/275)显著高于对照组+-++(13/252,χ2=4.94,P<0.05)。(3)血脂异常组中基因型联合10和11(基因型联合10～11)的TC均值显著高于本组中除基因型联合10及11(基因型联合1～9)的均值,apoAI/apoB均值显著低于本组中基因型联合1～9的均值。对照组中基因型联合10～11的apoAI/apoB水平也显著低于本组中基因型联合1～9。(4)E++/X+-/Ms++/M1/M2(基因型联合2)的TC在两组中都分别低于基因型联合10～11,apoAI/apoB在两组+-+-中都分别高于基因型联合10～11。(5)apoAI/apoB无论在血脂异常组还是在对照组都与TC、LDL-C负相关,与HDL-C正相关。结论:apoB基因EcoRI、XbaI、MspI位点和apoAI基因-75bp、+83bp各位点基因型多态联合中,基因型联合10及11与哈族人血脂异常相关。基因型联合2可能是预防血脂异常的因素。其中的机制可能与载脂蛋白基因变异引起apoAI/apoB的改变进而引起血脂的变化有关。     

高密度脂蛋白胆固醇与肝脂酶启动子514C/T多态性的关系

目的:探讨肝脂酶(HL)的基因启动子514C/T多态性与高密度脂蛋白胆固醇(HDL-C)间的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测203例高HDL-C患者和156名HDL-C正常对照者(对照组)的HL基因启动子514C/T多态性及其基因型,并探讨其与血脂水平的关系。结果:高HDL-C组HL基因启动子514C/T位点的基因型及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)。再按TG与TC水平将高HDL-C组再分成2组进行观察,高HDL-C组1[TG≥1.70 mmol/L和(或)TC≥5.72 mmol/L]的等位基因型频率与对照组比较,差异有统计学意义(P<0.05),而高HDL-C组2(TG0.05)。高HDL-C组1中CC型者除载脂蛋白A1(ApoA1)及ApoA1/ApoB100外,其他血脂指标均明显高于同基因型的对照组(P<0.05)。经过多元逐步Logistic回归分析,结果显示三酰甘油(TG)、总胆固醇(TC)与高HDL-C的发生有关(P     

The paraoxonase-1 codon 192 polymorphism is associated with fasting total cholesterol and LDL-cholesterol concentrations only in postmenopausal women. The REGICOR study.

Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-linked enzyme which appears to protect low-density lipoproteins (LDL) from oxidation. PON1 activity is associated with variation at the PON1 gene locus, specifically the common amino acid polymorphism at codon 192, for which the Q192 allele specifies low activity and the R192 allele specifies high activity. We investigated the association between the PON1 codon 192 polymorphism and fasting concentrations of glucose, lipids, lipoproteins and PON1 activity in 1380 subjects (724 men and 656 women). Several anthropometric and environmental factors were assessed in the present study. The PON1 Q192 allele frequency was 0.70 and 0.68 in men and women, respectively. In women, but not in men, significant associations were found between the PON1 codon 192 genotype and both total and LDL-cholesterol (p=0.004 and p=0.008, respectively), and subgroup analysis indicated that this relationship was predominant in postmenopausal women. Specifically, the Q192 allele was associated with increased total and LDL-cholesterol concentrations. Furthermore, these lipoprotein variables were higher among postmenopausal women with Q192/Q192 and Q192/R192 genotypes than in premenopausal women with the same genotypes (p<0.001). The findings suggest a gender-specific lipoprotein-genotype association with PON1 codon 192 genotypes in this study sample.     

郑州地区2型糖尿病肾功能衰竭患者芳香酯酶与基因Q192R多态性的关系

目的 探讨郑州地区汉族人群2型糖尿病慢性肾功能衰竭(DN-CRF)与血清芳香酯酶(ArE／PON1)活性及其192位基因多态性的关系。方法 通过检测2型糖尿病组(DM，121例)、DN-CRF组(123例)、健康对照组(127例)等观察对象的血清ArE／PONl活性及其192位基因多态性、血脂和脂蛋白等，进行分析研究。结果 郑州地区汉族人群中存在有ArE／PON1 192位等位基因Q与R，DN-CRF组Q、R基因频率为0．45和0．55，与DM、对照组比较，差异无统计学意义；两病例组患者血清酶活性均低于对照组，DN-CFR组降低幅度最大；DN-CFR组内RR基因型患者高密度脂蛋白胆固醇(HDL-C)、高密度脂蛋白2胆固醇(HDL2-C)水平低于QQ基因型，总胆固醇(TC)、甘油三酯(TG)和氧化型低密度脂蛋白(oxLDL)高于QQ基因型。结论 DN-CRF组ArE／PONl192位基因多态性与DM、健康对照组间虽差异无统计学意义，但不能排除DM合并DN-CRF与ArE／PON1的192位基因多态性有关；DN-CRF患者血清ArE／PON1活性降低，可能是DM合并DN的危险因素。     

凝血酶激活纤溶抑制物基因启动子区-438A/G多态性与脑梗死的关系

目的分析中国汉族人群凝血酶激活纤溶抑制物基因启动子区-438A/G (TAFI-438A/G)多态性与动脉粥样硬化性脑梗死(ACI)发病的关系。方法225 例ACI 患者(病例组)和184 例健康体检者(对照组)采用聚合酶链反应-限制性内切酶片段长度多态性分析方法(PCR-RFLP)检测TAFI-438A/G 多态性。结果TAFI-438A/G 基因型及等位基因频率在病例组与对照组之间无显著性差异。性别分层后,男性脑梗死组A等位基因频率为28.6%,高于对照组20.6% (P=0.039);AA基因型为9.0%,高于对照组1.9% (P=0.019);在女性中无显著性差异。结论TAFI-438A/G可能与男性脑梗死的发病有关,AA基因型可能增加男性脑梗死患病风险。     

Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy

Human serum paraoxonase 1 (PON1) is located on high-density lipoprotein and has been implicated in the detoxification of organophosphates, and possibly in the prevention of lipid peroxidation of low-density lipoprotein. PON1 has two genetic polymorphisms, both due to amino acid substitutions: one involving glutamine (Q genotype) and arginine (R genotype) at position 192, and the other involving leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effects of these polymorphisms, and of a polymorphism of the PON2 gene at position 310 (Cys/Ser; C and S genotypes respectively), on serum PON1 activity and concentration, plasma lipids and lipoproteins and glycaemic control in 93 individuals with type II diabetes with no complications and in 101 individuals with type II diabetes with retinopathy. Serum PON1 activity in the group with no complications [median 164.1 nmol.min(-1).ml(-1) (range 8.0-467.8)] was significantly higher than in the group with retinopathy [113.4 nmol. min(-1).ml(-1) (3.0-414.6)] (P<0.001), but the serum PON1 concentration was not different between the groups. The gene frequencies of the PON1-55 and PON1-192 polymorphisms and of the PON2-310 polymorphism were not different between the study populations. The PON1-55 and PON1-192 polymorphisms affected PON1 activity in the way described in a previous study of a control group and subjects with type II diabetes. The PON2-310 polymorphism also significantly affected serum PON1. PON1 activity was significantly higher in individuals with the PON2-310 CC genotype in both groups with type II diabetes, and the PON1 concentration was significantly higher in PON2-310 CC homozygotes with no complications than in the group with retinopathy. Neither the PON1-55 nor the PON1-192 polymorphism was correlated with the serum lipid or lipoprotein concentration in either group. In the group with retinopathy (but not the group with no complications), all three PON polymorphisms were correlated with glycaemic control, which was worse for the PON1-55 genotypes in the order MM>LM>LL (P=0.0032), for the PON1-192 genotypes in the order RR>QR>QQ (P=0.011) and for the PON2-310 genotypes in the order CC>CS>SS (P=0.010). Low serum PON1 activity in retinopathy may be related to an increased tendency for lipid peroxidation. Our findings thus raise the possibility that, in retinopathy, the PON2 gene may influence PON1, and that an inter-relationship between the PON1 and PON2 genes may influence glycaemic control in subjects with type II diabetes complicated by retinopathy.     

The paraoxonase promoter polymorphism (-107)T>C is not associated with carotid intima-media thickness in Sicilian hypercholesterolemic patients

BACKGROUND AND OBJECTIVES: Increased plasma low-density lipoprotein-cholesterol (LDL-C) levels in hypercholesterolemic subjects are associated with enhanced LDL oxidation that represents an additional risk for atherosclerotic disease. Human serum paraoxonase (PON1), a high-density lipoprotein (HDL) associated enzyme, has been shown to protect LDL from oxidation, thus playing an important role in reducing the risk of atherosclerosis. PON1 gene polymorphisms have been found to be associated with the variations in serum PON1 levels and activities, and with the risk for coronary artery disease (CAD). This study was performed to evaluate the contribution of the PON1 promoter (-107)T>C and the coding region Gln 192 Arg (Q192R) and Leu 55 Met (L55M) polymorphisms to the presence of carotid atherosclerosis in 208 Sicilian subjects with primary hypercholesterolemia. METHODS: Carotid artery intima-media wall thickness (IMT) was measured as an indicator of early atherosclerotic disease. The subjects were classified according to whether they have a normal (1 mm) IMT. Subjects were also investigated for physical and biochemical parameters, including PON1 activity. RESULTS: No significant differences were detected among the PON1 genotypes with respect to age, sex, BMI, plasma lipids, systolic blood pressure in both groups of patients. There were significant differences between PON1 genotypes with respect to PON1 activity. The 192QQ, 55MM and (-107)TT genotypes showed lower PON1 activity compared to the RR, LL and CC genotypes. The PON1 (-107)T>C genotype distribution in both IMT groups showed no significant differences in percentage of TT, CT and CC genotypes. Similar results were obtained analyzing the Q192R and L55M genotype frequencies. Stepwise forward logistic regression analysis confirmed the lack of association between PON1 genotypes and carotid abnormalities. CONCLUSIONS: In conclusion, our data provided no evidence of a significant association between either PON1 promoter (-107)T>C or coding region, Q192R and L55M, polymorphisms and early carotid atherosclerosis in Sicilian hypercholesterolemic subjects.     

青年人动脉粥样硬化性脑梗死与载脂蛋白E、B基因多态性的关系

背景动脉粥样硬化性脑梗死与载脂蛋白E、B基因多态性的研究有所报道,然而结果不尽相同.载脂蛋白E、B基因多态性与青年人动脉粥样硬化性脑梗死的相关性研究国内未见报道.目的应用聚合酶链反应技术分析载脂蛋白E、B基因多态性对青年动脉粥样硬化性脑梗死发病的意义及其相关性.设计以青年动脉粥样硬化性脑梗死患者为研究对象,病例-对照分析.单位中国医科大学盛京医院神经内科.对象实验于1998-01/2000-12中国医科大学盛京医院完成.选取神经内科动脉粥样硬化性脑梗死患者36例作为脑梗死组,男30例,女6例,平均年龄(41.6±6.54)岁;对照组为100例体检健康的沈阳籍汉族青年,男66例,女34例,平均年龄(36.16±6.12)岁.方法两组患者于空腹12 h后抽取静脉血8 mL,测定血清脂类及载脂蛋白.采用聚合酶链反应技术检测载脂蛋白E和载脂蛋白B的基因多态性;酶法测定血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇含量;免疫比浊法测定血清载脂蛋白AI.B浓度;酶联免疫法测定血清脂蛋白a的含量.主要观察指标①载脂蛋白E、B基因型频率在两组人群中的分布特征.②载脂蛋白E和载脂蛋白B基因多态性与血脂、脂蛋白和载脂蛋白的含量的关系.③载脂蛋白E、B基因型与青年人动脉粥样硬化性脑梗死发病中的关联强度.结果①脑梗死组患者ε3/4型频率为36.1%,ε2/4型频率为27.7%;对照组分别为12%和7%;梗死组ε4等位基因频率为0.320,明显高于对照组的0.095(P＜0.05).②脑梗死组患者三酰甘油、总胆固醇、脂蛋白a含量明显高于对照组,高密度脂蛋白胆固醇含量显著低于对照组(P＜0.05～0.001).③ε4等位基因使血清三酰甘油、总胆固醇、血清脂蛋白a含量增高、致高密度脂蛋白胆固醇含量降低的相对风险率依次为8.23,4.85,4.39,29.9(P＜0.01～0.001).④载脂蛋白B基因XbaⅠX+X-亚组的载脂蛋白A Ⅰ含量为(1.01±0.30)g/L,明显低于X-X-亚组的(1.33±0.15)g/L(t=2.55,P＜0.05);X+X-亚组的血清脂蛋白a含量为244.3 mg/L,与对照组的含量183.0 mg/L相比,差异有显著性意义(t=4.50,P＜0.01).⑤脑梗死组患者中ε3与X+X-同时存在者3例,与X-X同时存在10例;ε4与X+X-同时存在者2例,与X-X-同时存在19例,ε4与X-X-并存时动脉粥样硬化性脑梗死发病风险率为2.85(x2=1.52,P＞0.05).结论载脂蛋白E等位基因ε4是青年人动脉粥样硬化性脑梗死的一种遗传易感性因子;XbaⅠ X+X-可能是另一种遗传标记;载脂蛋白E与载脂蛋白B基因型并存时与年青人动脉粥样硬化性脑梗死的关系需进一步研究.     

心肌梗死患者对氧磷酶-1 Q/R192基因多态性及活性检测的临床意义

目的探讨心肌梗死（AMI）患者对氧磷酶-1（PON1）Q/R192基因多态性及其活性检测的临床意义。方法分别采用紫外线分光光度法和聚合酶链式反应-限制性片段长度多态性（PCR-RELP）法检测65例AMI患者和70名健康体检者PON1活性及PON1Q/R192基因多态性。结果 AMI组血清PON1活性[（78.56±16.69）U/mL]明显低于健康对照组[（118.65±30.25）U/mL]（P〈0.01）。AMI组与健康对照组3种基因型及2种等位基因频率分布差异无统计学意义（P〉0.05）;AMI组与健康对照组间不同PON1 Q/R192基因型间血清PON1活性相比差异有统计学意义（P〈0.01）;AMI组内及健康对照组内PON1 Q/R192不同基因型间血清PON1活性相比差异无统计学意义（P〉0.05）。结论血清PON1活性降低是AMI的危险因素之一;PON1Q/R192基因多态性与AMI的发生无相关性。     

Polymorphisms of pon1 and pon2 genes in hemodialyzed patients

Objectives

Q192R, L55M and -108C>T polymorphisms of pon1 gene affect PON1 paraoxonase activity while S311C polymorphism of pon2 gene might be associated with coronary heart disease. The aims of this study were to determine the frequencies of Q192R, L55M, -108C>T and S311C polymorphisms in hemodialyzed patients and to examine the relationship between pon1 gene polymorphisms and PON1 paraoxonase activity in those patients.

Design and Methods

The study included 238 control subjects and 263 hemodialyzed patients.

Results

PON1 paraoxonase activity was lower in patients. Genotype frequencies were different between two compared groups only for L55M polymorphism, with control group having higher frequency of MM genotype. Polymorphisms of pon1 gene were associated with significant variation in PON1 paraoxonase activity in both study groups.

Conclusion

Our results suggest that Q192R, L55M and -108C>T polymorphisms are not by itself the causal factors leading to the lower PON1 paraoxonase activity in hemodialyzed patients.     

Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population.

BACKGROUND: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1Q192R, have been studied. However, inconsistencies regarding the above-mentioned polymorphism obscure its association with vascular disease. METHODS: Using a two-substrate (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R phenotypes in 261 middle-aged subjects: 156 patients with angiographically assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control group. The PON1(192) phenotype was predicted from examination of the two-dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the antimode of the histogram of the ratio of diazoxonase/paraoxonase activity. RESULTS: The PON1Q192R phenotype frequencies in 113 patients with occlusion >50% (coronary artery disease-positive, CAD+ group) vs. control population were as follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082); chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase) activities in the CAD+ patients when compared to the control population. According to logistic regression analysis, POase activity was a better predictor of coronary disease onset compared with DZOase activity measurements and PON1Q192R phenotyping. CONCLUSIONS: We conclude that enzyme activity (within a particular phenotypic group) is more important than phenotype alone in predicting susceptibility to coronary artery disease.     

基质金属蛋白酶-1基因多态性与动脉粥样硬化性脑梗死相关性研究

目的研究基质金属蛋白酶-1(MMP-1)基因多态性与动脉粥样硬化性脑梗死(ACI)的相关性。方法检测95例ACI患者(不稳定斑块组51例、稳定斑块组44例)和58例体检健康者外周血MMP-l水平及MMP-l基因启动子区上游-1 607bp处1G或2G单核苷酸多态性,比较不同MMP-l基因型频率和外周血MMP-l水平。结果不稳定斑块组2G/2G基因型频率和2G等位基因频率显著高于稳定斑块组,二者2G/2G基因型频率与2G等位基因频率均显著高于对照组,且不稳定斑块组和稳定斑块组外周血MMP-l水平均高于对照组(P<0.05)。结论 MMP-1基因多态性和外周血MMP-1水平均与ACI具有相关性。