细胞间黏附分子-1基因469K/E多态性与心肌梗死的关系探讨

目的探讨细胞间黏附分子-1(ICAM-1)基因K469E多态性与中国汉族人群心肌梗死(MI)发病率的关系.方法采用巢式PCR技术对206例(MI89例)进行ICAM-1基因K469E多态性检测分析.结果基因型频率符合Hardy-Weinberg平衡,MI组和对照组KK、KE、EE基因型频率分别是37.1%、43.8%、19.1%和27.4%、38.5%、34.2%;等位基因K、E频率分别是59.00%、41.00%和46.58%、53.42%,两组差异有统计学意义.回归分析显示,K等位基因、吸烟增加了MI发病的危险,并对MI的发生具有协同作用.结论中国汉族人群存在ICAM-1基因K469E多态性,ICAM-1基因469K/E多态性与MI的发病有关,K等位基因可能为其独立危险因素之一.     

低密度脂蛋白受体基因NcoI多态性与老年人心肌梗死的关系

目的探讨低密度脂蛋白受体基因(LDLR)NcoI多态性与心肌梗死(MI)的相关性,并对其与血脂的关系进行分析。方法用聚合酶链反应(PCR)技术检测102例辽宁藉汉族健康人和84例老年MI患者的LDLR基因NcoI多态性及含量。结果LDLR基因NcoI等位基因频率健康人N+为0.667,MI组基因N+为0.768,MI组比对照组明显增高(P<0.05);血清TC、LDLC、TG及LP(a)水平亦明显增高(P<0.05)。结论NcoI多态性的N+型等位基因与MI的发生密切相关。     

内源性高甘油三酯血症患者载脂蛋白AⅠ基因MspI酶切位点多态性

探讨中国人内源性高甘油三酯血症患者载脂蛋白AⅠ基因MspI酶切位点变异频率及其对血脂、载脂蛋白水平的影响。应用多聚酶链反应对成都地区汉族 2 5 5例正常人和 134例内源性高甘油三酯血症患者apoAⅠ基因启动子 (- 78bp)及内含子I(+83bp)两个MspI限制性片段多态性进行分析。内源性高甘油三酯血症组及对照组载脂蛋白AⅠ基因MspI的多态性以G/G基因型占优势。载脂蛋白AⅠ基因启动子区MspI酶切位点A等位基因频率内源性高甘油三酯血症组显著高于对照组 (0 .35 0比 0 .2 73,P <0 .0 5 ) ,并显著高于欧美的白种人 (0 .30 0vs 0 .12 0～ 0 .191,P <0 .0 1) ,而 +83bpT等位基因则未见差异。在所研究对象中具有A/A基因型者血清甘油三酯水平、甘油三酯 /高密度脂蛋白胆固醇比值及载脂蛋白CⅢ水平较具有G/G及G/A基因型者显著升高 (P <0 .0 5 ) ,血清载脂蛋白CⅡ水平有增加趋势 (P >0 .0 5 )。载脂蛋白AⅠ基因启动子 (- 78bp)MspI酶切位点的突变与中国人内源性高甘油三酯血症有一定关联 ,载脂蛋白AⅠ基因A/A基因型对血清甘油三酯、载脂蛋白CⅡ水平及甘油三酯 /高密度脂蛋白胆固醇比值的升高有一定影响。     

内源性高甘油三酯血症患者载脂蛋白AⅠ基因MspI酶切位点多态性

探讨中国人内源性高甘油三酯血症患者载脂蛋白AⅠ基因MspI酶切位点变异频率及其对血脂、载脂蛋白水平的影响.应用多聚酶链反应对成都地区汉族255例正常人和134例内源性高甘油三酯血症患者apoAⅠ基因启动子(-78 bp)及内含子I(+83 bp) 两个MspI限制性片段多态性进行分析.内源性高甘油三酯血症组及对照组载脂蛋白AⅠ基因M spI的多态性以G/G基因型占优势.载脂蛋白AⅠ基因启动子区MspI酶切位点A等位基因频率内源性高甘油三酯血症组显著高于对照组(0.350比0.273,P<0.05),并显著高于欧美的白种人(0.300 vs 0.120～0.191, P<0.01),而+83 bp T 等位基因则未见差异.在所研究对象中具有A/A基因型者血清甘油三酯水平、甘油三酯/高密度脂蛋白胆固醇比值及载脂蛋白CⅢ水平较具有G/G及G/A基因型者显著升高(P<0.05),血清载脂蛋白CⅡ水平有增加趋势(P>0.05).载脂蛋白AⅠ基因启动子(-78 bp)MspI酶切位点的突变与中国人内源性高甘油三酯血症有一定关联,载脂蛋白AⅠ基因A/A基因型对血清甘油三酯、载脂蛋白CⅡ水平及甘油三酯/高密度脂蛋白胆固醇比值的升高有一定影响.     

同型半胱氨酸代谢相关酶基因多态性与心肌梗死关系的研究

目的研究同型半胱氨酸代谢相关酶亚甲基四氢叶酸还原酶(MTHFR)、胱硫醚-β-合成酶(CBS)及蛋氨酸合成酶(MS)基因多态性与心肌梗死(MI)相关性。方法应用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)和聚合酶链反应(PCR)产物直接电泳技术,检测121例MI患者(患者组)和500例健康人(正常对照组)的MTHFR C677T、CBS 844 ins68和MS A2756G基因多态性。结果MTHFR C677T基因型分别为:CC野生型、CT杂合型、TT突变型。其在患者组分布频率分别为14.0%、46.3%、39.7%,T等位基因频率为62.85%,C等位基因频率为37.15%;正常对照组中为35.6%、44.0%2、0.4%,T等位基因频率为42.4%,C等位基因频率为57.6%。两组间各基因频率及等位基因频率比较差异均具有统计学意义(P<0.05)。而CBS 844ins 68和MSA2756G的基因型频率分布,两组间差异均无统计学意义(P>0.05)。结论MTHFR基因TT基因型,T等位基因与MI具有相关性;而CBS 844 ins68及MS A2756G基因多态性可能与MI发生无直接相关性。     

屏氧酶192基因多态性与血脂及心肌梗死的关系

目的 :研究屏氧酶 192谷氨酸 /精氨酸 (PON192 ,Gln/Arg)基因多态性与血浆脂质水平及心肌梗死(MI)的关系。方法 :应用多聚酶链反应 限制性内切酶片段长度多态性 (PCR RFLP)技术检测 132例MI与相同例数正常人PON 192基因多态性 ,血浆脂质水平测定按常规进行。结果 :发现PON 192基因型有三种 ,即纯合子突变型 (BB) ,杂合子突变型 (AB) ,正常型 (AA)。正常对照组中AA型频率 17.6 % ,AB型频率 4 5 .3% ,BB型频率37.1%。A等位基因频率为 4 5 .2 % ,B等位基因频率为 5 4 .8%。MI组AA型频率 10 .2 % ,AB型频率 4 1.3% ,BB型频率 4 8.5 %。A等位基因频率为 30 .7% ,B等位基因频率为 6 9.3%。两组对比等位基因频率差异有显著性意义。高密度脂蛋白水平在两组间差异无显著性意义。结论 :MI患者PON 192 ,B等位基因频率明显高于正常对照组 ,说明PON 192基因突变与MI的发生密切相关     

心肌梗死患者载脂蛋白B基因多态性

为研究载脂蛋白Ｂ基因多态性与动脉粥样硬化的关联,选择健康体检者８４人和确诊为心肌梗死患者８４人为对象,进行载脂蛋白Ｂ基因多态性的研究。用聚合酶链反应检测心肌梗死患者和正常人的载脂蛋白Ｂ基因上３个位点的遗传多态性标记,结果显示,心肌梗死患者组载脂蛋白Ｂ基因上的ＸｂａＩ酶切位点上Ｘ＋等位基因相对频率明显高于正常组（Ｐ〈０．０５）。而ＥｃｏＲＩ和ＭｓｐＩ酶切位点的Ｅ＋和Ｍ＋等位基因相对频率与正常人组无明     

急性心肌梗死患者脂蛋白脂肪酶基因Ser447Stop的多态性研究

目的 探讨中国人群中脂蛋白脂肪酶基因Ser447Stop多态性与急性心肌梗死的相关性.方法 应用PCR和限制性片段长度多态性分析的方法测定86例急性心肌梗死患者和90例对照组脂蛋白脂肪酶基因Ser447Stop多态性.结果 急性心肌梗死组的CG GG基因型频率显著低于对照组(分别为0.174和0.422,P<0.05).急性心肌梗死组的G等位基因频率为0.087,亦显著低于对照组的0.217.急性心肌梗死亚组间的分析显示,血脂异常组CG GG基因型与G等位基因频率均显著低于血脂正常组(P<0.05).结论 脂蛋白脂肪酶基因Ser447Stop多态性与急性心肌梗死有一定的相关性,G等位基因可能是急性心肌梗死的一个保护性因素.     

老年心肌梗死与载脂蛋白E基因多态性相关性研究

目的　 研究老年心肌梗死 (MI)与载脂蛋白E(ApoE)基因多态性的相关关系以及ApoE对血脂水平的影响。　 方法　应用聚合酶链反应—限制性片段长度多态性 (PCR RFLP)方法 ,测定 93例老年MI患者和 10 9例对照者的ApoE基因型 ;血脂水平按常规方法测定。　 结果　本研究发现 4种ApoE基因型 :E 3/3、E 3/2、E 4/3及E 4/2。老年MI组ApoE 4/3基因型和ε4等位基因频率均显著高于对照组 (P <0 0 1) ;老年MI组总胆固醇 (TC)、低密度脂蛋白胆固醇 (LDL C)显著高于对照组 (P <0 0 1) ;在老年MI组ApoE基因各亚型之间 ,TC和LDL C水平之间存在统计学差异 (P <0 0 5 )。　 结论　ApoE基因多态性与老年MI的发生发展有关并影响血脂的代谢水平 ;ε4等位基因可能是老年MI重要的遗传易患因素之一。     

冠心病患者血管紧张素转换酶基因多态性分析

应用PCR技术对80例冠心病患者(冠心病组)和100例健康查体者(对照组)脂类代谢参数与ACE基因插入/缺失(I/D)型多态性进行检测,并进行相关性分析.结果冠心病组血脂水平明显高于对照组,P均＜0.05;对照组血浆apoB水平与AcE基因型无明显相关性;而冠心病组apoB水平与D等位基因数目明显相关,血浆apoB水平在D等位基因纯合子中最高.认为ACE基因多态性在冠心病发生中起重要作用,机制可能为改变血浆载脂蛋白谱.     

Polymorphisms in the apolipoprotein B-100 gene: association with plasma lipid concentration and coronary artery disease

BACKGROUND: The aim of this study was to investigate the association of apolipoprotein B gene polymorphisms with coronary artery disease and lipid levels in Indians. METHODS AND RESULTS: One hundred patients of angiographically proven atherosclerotic coronary artery disease and one hundred age- and sex-matched control subjects (treadmill negative) were included in the study. Serum lipids including cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, and apolipoprotein B were analyzed. Genomic DNA was extracted and the apolipoprotein B 3' hypervariable region amplified by polymerase chain reaction. Regions carrying Xba1, EcoR1, and Msp1 restriction sites present in the apolipoprotein B gene were amplified and digested separately by the respective enzymes. Restriction fragment length polymorphism analysis showed that EcoR1 with the R+/R+ genotype was significantly more common in patients with coronary artery disease. Overall, the genotypes EcoR1+/+, Msp1+/+, Xba1+/+ and Eco R1+/+ Msp1+/-, Xba1-/- were significantly more common in patients as compared to controls (p<0.05). When gene polymorphisms were compared with lipid abnormalities, the genotypes EcoR1+/+, Xba1-/-, and Msp1+/+ were more frequent in patients with elevated apolipoprotein B and very low-density lipoprotein levels. On the other hand, these genotypes were less common in patients with increased total cholesterol and low-density lipoprotein levels. When we studied the individual alleles of the variable number of tandem repeats region, we observed that allele 34 was significantly increased in patients with coronary artery disease as compared to controls. Allele 36 was present with a frequency of 1% in controls while it was totally absent in patients. CONCLUSIONS: This study identifies the apolipoprotein B gene polymorphism associated with coronary artery disease. An association between apolipoprotein B gene polymorphisms and elevated apolipoprotein B and very low-density lipoprotein levels was observed. However, there was no positive association with other elevated lipid levels in North Indians from Uttar Pradesh.     

Lack of association between genetic variations of apo A-I-C-III-A-IV gene cluster and myocardial infarction in a sample of European male: ECTIM study.

The goal of the present study was to compare the allele frequency of four polymorphisms at the apo A-I C-III A-IV cluster gene locus-ApoA-I: XmnI and PstI; ApoC-III: SstI; ApoA-IV: XbaI-between male patients who had had a myocardial infarction (n= 614) and matched controls (n = 764). The association with a number of lipid lipoprotein, apolipoprotein and lipoprotein particle variables was also assessed. Patients and subjects were recruited in Belfast, Lille, Strasbourg and Toulouse in the framework of the ECTIM study. In the control group, the frequencies of the different polymorphic alleles were homogeneous among recruitment centres suggesting the absence of any European North to South gradient for these cluster polymorphisms. There was no evidence for a significant difference in allelic distribution between cases and controls suggesting that apo A-I, C-III, A-IV gene cluster polymorphisms do not explain MI survival in this sample of European men. There was no statistically significant association between apo A-I C-III A-IV cluster gene polymorphisms and lipid, lipoprotein, apolipoprotein, and lipoprotein particle levels. In conclusion, in the ECTIM study, the apo A-I, C-III, A-IV gene cluster polymorphism is associated with neither circulating plasma variables nor MI survival.     

DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease

Elevated plasma levels of low density cholesterol and their major apolipoprotein (apo B) are associated with an increased risk of coronary artery disease (CAD). We have examined allele frequencies of restriction fragment length polymorphisms (RFLP) of the apo B gene in 111 male Caucasians with premature CAD (mean age 49 +/- 7 years) and in 122 elderly Caucasian males (mean age, 73 +/- 5 years), free of clinical cardiovascular disease. The rare allele (R1) of the EcoR1 RFLP in exon 29, resulting in an amino acid change (Glu----Lys4154) was seen more frequently in CAD than in controls (0.270 vs 0.207, P less than 0.05). The R1 RFLP and the MspI insertion polymorphisms (MI) within the 3' hypervariable region (HVR) were observed together in 87% and are likely in linkage disequilibrium. The MI RFLP were slightly more frequent in CAD than control (0.239 vs. 0.211, P = 0.08). A second MspI RFLP in exon 26 results in an amino acid change (Arg----Glu3611); the rare allele M2 was seen more frequently in patients than in controls (0.150 vs. 0.057, P less than 0.005). No significant differences in allele frequencies were observed for the Xba1 RFLP in exon 26 (0.500 vs. 0.529, P = ns) or for the PvuII RFLP near the 5' end (P2) (0.105 vs. 0.088, P = ns). No statistically significant differences in lipid, lipoprotein cholesterol or apolipoproteins A-I and B were observed in patients or in controls. Two of the RFLPs examined (R1 and M2) result in changes in amino acid sequence and their allele frequencies are increased in CAD cases when compared with controls. Genetic variability within the apo B gene may thus contribute to cardiovascular risk. The physiological effects of individual mutations within apo B remain to be determined. It is unlikely, however that the single site polymorphisms examined in this study, will impart further information about CAD risk than conventional lipid parameters.     

Parental history of myocardial infarction: lipid traits, gene polymorphisms and lifestyle

To investigate the relationship between parental history of myocardial infarction (MI), lipid traits and gene polymorphisms involved in lipid metabolism, we examined Dutch men and women, who were selected from a large population-based study. Subjects whose father (n=112), mother (n=115) or both parents (n=115) suffered from a premature MI presented with significantly higher apolipoprotein B (apo B) levels than subjects without a parental history (n=114). Genetic analyses revealed that the apo E4 isoform and the D9N mutation of lipoprotein lipase (LPL) were more frequent among subjects with a parental history (P< or =0.05). A similar trend was found for the LPL N291S mutation. In contrast, the LPL S447X mutation and polymorphisms at the cholesteryl ester transfer protein (TaqIB) and apo CIII (SstI) loci proved to be noninformative. Body mass index and lifestyle could not explain differences in apo B levels between parental history groups. In contrast, the apo E polymorphism and the LPL D9N mutation accounted for some, but not all, of the higher apo B levels in subjects with a parental history. Therefore, other genetic or lifestyle-related factors must be responsible for the increased levels of apo B in individuals with a family history of myocardial infarction.     

Apolipoprotein B gene variants are involved in the determination of serum cholesterol levels: a study in normo- and hyperlipidaemic individuals

We have investigated the frequencies of 3 restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene in normo- and hyperlipidaemic individuals. In individuals with type III hyperlipidaemia, the allele frequency for the RFLP detected with XbaI was significantly different from the allele frequency in normolipidaemic individuals and in those with other types of hyperlipidaemia. No significant difference in allele frequency was found among these groups for the RFLPs detected with MspI or EcoRI. Within a sample of 62 normolipidaemic individuals, homozygotes for the X2 allele (cutting site) of the XbaI RFLP had a significantly higher serum cholesterol level than homozygotes for the XI allele, with individuals of the genotype X1X2 having an intermediate value (X2X2 mean 5.71 mmol/l, X1X1 mean 4.81 mmol/l, X1X2 mean 5.30 mmol/l). There were also significant differences in serum triglyceride levels in individuals with different XbaI genotypes. In these normolipidaemic individuals there was no correlation between the EcoRI and MspI RFLP genotypes and levels of any serum lipid variable. Information from the XbaI and EcoRI RFLPs was used in conjunction to define apo B haplotypes. These haplotypes are a more precise measure of the genotypic variation, and they explain a greater fraction of the serum cholesterol and triglyceride levels than the single-site polymorphisms considered separately. This study suggests that variations in the gene for apo B are associated with the determination of serum cholesterol and triglyceride levels both in patients with type III hyperlipidaemia and in the normal population.     

Lipoproteins and apolipoproteins in young male survivors of myocardial infarction

Plasma and lipoprotein cholesterol, triglycerides, apolipoproteins (apo) A-I, A-II, B and phospholipid concentrations were measured at 10 days and 4 months after myocardial infarction (MI) in 60 young Kuwaiti male MI survivors below the age of 40 years. Controls were matched for age, relative weights, smoking, dietary habits and physical activities. The young MI survivors had significantly higher levels of total and LDL-cholesterol, and ratios of LDL/HDL- and LDL/HDL2-cholesterol. Total VLDL and LDL triglycerides, and phospholipids were also elevated in MI survivors compared to controls. Similarly, plasma and LDL-apo B as well as the ratios of apo B/apo A-I were higher in the MI group. There was no significant change in the levels of VLDL and HDL3-cholesterol and of apo A-II in these patients compared to their controls. Concentrations of HDL- and HDL2-cholesterol and of plasma and HDL apo A-I were significantly lower in the young MI survivors compared to the control subjects. The better discriminating lipoproteins and apolipoproteins in MI patients in descending order were HDL2-cholesterol greater than apo B greater than apo A-I greater than VLDL-triglyceride greater than HDL-cholesterol greater than LDL/HDL2-cholesterol greater than triglycerides. The data indicate that measurement of HDL2-cholesterol, apo B and apo A-I may be useful indicators in assessing coronary artery disease risk than triglycerides (TG), total cholesterol (TC), LDL-cholesterol and HDL-cholesterol.     

110例心肌梗死患者载脂蛋白E基因多态性

为探讨载脂蛋白Ｅ基因型和心肌梗死之间的关系,采用聚合酶链反应－限制性片长多态性分析１１０例心肌梗死患者和１３１例健康对照者的载脂蛋白Ｅ基因型及其在两组人群中的不同分布。结果发现对照组和心肌梗死组Ｅ３／３基因型发生频率最高,占整个样本的７０％,含载脂蛋白Ｅ３的杂合子居中,占整个样本的２５．３％,Ｅ４／４基因型的发生频率最低。     

Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction

High level of total homocysteine (tHcy) is a risk factor for coronary artery disease (CAD), but the mechanism is not known. The serum concentration of tHcy, total cholesterol, high density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (apo A-I) and the concentration of folate in whole blood were measured in 107 patients with first acute myocardial infarction (MI) and 103 controls. The level of whole blood folate was lower and that of tHcy higher in cases than in controls. An increase of 50 nmol/l whole blood folate was associated with an OR for MI of 0.75, and an increase of 5 micromol/l tHcy with an OR for MI of 1.57. Correlations were observed between the levels of whole blood folate and tHcy and between whole blood folate and alcohol intake, and in MI cases, between tHcy, HDL-C, and apo A-I as well as between HDL-C and alcohol intake. The number of cigarette smokers was higher among cases than controls. In smokers, the level of tHcy was higher and that of whole blood folate lower than in non-smokers. After adjustment for smoking, the whole blood folate and tHcy-associated risks of MI became non-significant. We conclude that smoking may affect folate status and tHcy level adversely. The risk of MI in smokers may at least partly be attributed to hyperhomocysteinemia or low folate.     

血小板受体GPⅢa基因P1A1/P1A2多态性与心肌梗塞关系的研究

冠心病心肌梗塞(MI)与凝血纤溶系统的关系一直广受关注.近来,有报道称美国白种人血小板受体GPⅢa基因的PIA1/PIA2多态性与MI发病相关.本研究运用RFLP和ASO技术对82例MI患者和68例对照进行该多态性的检测,并与50例美国健康白种人作比较.结果显示150例中国人的GPⅢa多态基因型均为P1A1/P1A1,与美国白种人有显著差别.表明中国人群血小板受体GPⅢa基因的PlA1/PlA2多态性与MI发病无相关性.