【作者】 张钱林；

【导师】 杜小平；

【作者基本信息】 中南大学 ， 神经病学， 2009， 硕士

【摘要】 目的:(1)探讨中国湖南汉族人群中髓过氧化物酶(Myeloperoxidase,MPO)基因-463G＞A和-638C＞A多态性与动脉粥样硬化性脑梗死和高血压脑出血的相关性。(2)探讨中国湖南汉族人群中MPO基因-463G＞A和-638C＞A多态性与血脂、血压、血糖和颈动脉粥样硬化斑块的关系。方法:应用等位基因特异引物PCR(ASP-PCR)技术检测273例动脉粥样硬化性脑梗死(cerebral infarction,CI)、205例高血压脑出血(intracerebral hemorrhage,CH)患者和213例在年龄、性别方面相匹配的健康体检者的MPO基因-463G＞A和-638C＞A多态位点的基因型及等位基因的频率分布,同时检测研究对象的血脂、血糖、血压、BMI及IMT水平。采用HWE软件检验基因型的Hardy-Weinberg平衡吻合度,采用SPSS13.0统计软件对所获得的数据进行相应的统计学分析。结果:(1)中国湖南汉族人群中存在MPO基因-463G＞A和-638C＞A多态性,在正常对照人群中MPO基因-463G＞A多态位点的等位基因频率是:G为0.761,A为0.239,-638C＞A多态位点的等位基因频率是:C为0.845,A为0.155。脑梗死组、脑出血组MPO基因-463G＞A和-638C＞A多态位点的基因型和等位基因频率分布与对照组比较无显著性差异(P＞0.05),logistic回归分析未发现MPO基因-463G＞A和-638C＞A多态位点的基因型增加或减少脑卒中发生的风险(P＞0.05)。(2)MPO基因-463G＞A和-638C＞A多态位点的基因型及等位基因频率在合并高血压病的CI亚组和未合并高血压病的CI亚组之间分布无显著性差异(P＞0.05),在有无家族史的CI亚组、CH亚组之间分布无显著性差异(P＞0.05)。(3)在CI组中MPO基因-463G＞A的GA和AA亚组与GG纯合子亚组相比,HDL-c水平显著升高,LDL-c水平显著降低,差异均有统计学意义(P＜0.05)。在CH组中MPO-463G＞A的GA杂合子亚组与GG纯合子亚组相比,LDL-c水平显著降低,差异有统计学意义(P＜0.05)。在CH组中,MPO-638C＞A位点的AA纯合子亚组与GG、GA相比,HDL-c水平显著降低,差异有统计学意义(P＜0.05)。(4)CI合并糖尿病亚组CA、AA基因型频率和A等位基因频率明显高于对照组,差异有统计学意义(P＜0.05)。(5)MPO基因-463G＞A多态分布在CI+AP(有斑块)亚组和CI+NAP(无斑块)亚组之间比较,GA、AA基因型频率和A等位基因频率前者明显小于后者,差异有统计学意义(P＜0.05);MPO基因-463G＞A多态分布在CH+AP(有斑块)亚组和CH+NAP(无斑块)亚组之间比较,GA、AA基因型频率明显小于后者,差异有统计学意义(P＜0.05),但两组之间等位基因频率分布无显著差异(P＞0.05)。(6)脑梗死组的“-463 GG”型亚组中,“-638CA+AA”基因型携带者合并DM的构成比显著高于“-638CC”基因型携带者(P＜0.05);脑梗死组的“-463GG”型亚组中,“-638CA+AA”基因型携带患者的LDL-c水平显著高于“-638CC”基因型携带患者(P＜0.05)。结论:(1)MPO基因-463G＞A和-638C＞A多态性可能与中国湖南地区汉族人群脑梗死和脑出血的发生无相关性。(2)MPO基因-463G＞A多态性可能与中国湖南汉族脑梗死人群颈动脉粥样斑块有关。(3)MPO基因-463G＞A和-638C＞A位点的A等位基因与中国湖南汉族人脑卒中患者的高HDL血症和低LDL血症有关。(4)MPO基因-463G＞A与-638C＞A多态性对脑梗死患者罹患高LDL血症和糖尿病风险存在交互作用。更多还原

【Abstract】 Objective:To investigate the association between the MPO -463G＞A and -638C＞A polymorphisms and stroke,hypertension, atherosclerosis and also the metabolism of the blood lipids.Methods:The genotypes of 273 patients with atherosclerotic cerebral infarction,205 patients with primary cerebral hemorrhage and 213 sex-and-age-matched health controls were detected by ASP-PCR. Serum lipid concentrations were determined by enzymatic analytical chemistry.The HWE software was used to check the goodness of fit of Hardy-Weinberg balance of the genotypes.All date was analyzed by SPSS 13.0.Result:(1)-463G＞A and -638C＞A of MPO polymorphisms exist in Chinese people of Hunan area,with the allele frequencies 0.761/0.239 for -463G＞A and 0.845/0.155 for -638C＞A respectively.No significant differences were observed in genotypes and allele frequencies between stroke patients and controls for MPO -463G＞A,-638C＞A(P＞0.05).Logistic regression analysis suggested that neither any genotypes no any alleles could increase the risk of onset of stroke(P＞0.05).(2)The difference of the frequency of MPO -463G＞A,-638C＞A genotypes and alleles between the hypertension subgroup and the nohypertension subgroup of the CI and CH group were not significant(P ＞0.05).The similar result was observed between the family history and no family history of CI and CH group(P＞0.05).(3) The mean serum level of HDL-c of -463G＞A GA carriers and AA carriers was higher than GG carriers in CI group(P＜0.05);The mean serum level of LDL-c of -463G＞A GA+AA carriers and AA carriers was lower than GG carriers in CI and CH group(P＜0.05).(4)The difference of the frequency of MPO -638C＞A genotypes and alleles between the CI+DM subgroup and the controls was significant(P＜0.05).(5)The difference of the frequency of MPO -463G＞A genotypes and alleles between the CI+AP subgroup and the CI+NAP subgroup was significant(P＜0.05);The difference of the frequency of MPO -463G＞A genotypes and alleles between the CH+AP subgroup and the CH+NAP subgroup was significant(P＜0.05).(6)The incidence rate of DM of -638CA+AA and -638CC carriers had significant difference in -463 GG subgroup;The mean serum level of LDL-c of -638CA+AA carriers was higher than CC carriers in -463 GG subgroup(P＜0.05).Conclusion:(1) There is probably no association between the MPO -463G＞A and -638C＞A polymorphism and CI or CH in han population in Hunan province. (2)There is probably some association between the MPO -463G＞A polymorphism and the carotid artery atherosclerosis plaque in han population in Hunan province.(3)There is probably some association between the MPO -463G＞A and -638C＞A polymorphism and the metabolism of HDL-c and LDL-c in Chinese han population.A allele might be an important factor of affecting the serum levels of HDL-c and LDL-c.(4)MPO -463G＞A and -638C＞A polymorphism have a possible interaction in their effects on the presence of LDL concentrations and DM.更多还原