对氧磷酶2基因S311C多态性与脑出血关系的研究

目的 探讨对氧磷酶2（paraoxonase 2,PON2）基因多态性与脑出血（intracerebral hemorrhage,ICH）的关系.方法 用聚合酶链反应-限制性片段长度多态性分析法（PCR-RFLP）探查PON2基因S311C多态性在脑出血组和对照组的基因频率.结果 中国湖南人存在PON2 S311C基因多态性,S/C 0.727/0.273 脑出血组患者PON2基因的基因型及等位基因频率与对照组比较均没有显著差异（P＞0.05） 脑出血组内各基因型及等位基因频率的血糖、血脂水平比较均未发现有显著性差异（P＞0.05）.结论 PON2基因第311位密码子的多态性与脑出血无关.     

早老素-2基因启动子区-1560A/del位点多态性与散发性阿尔茨海默病的相关性研究

目的探讨早老素-2（PSEN2）启动子区-1560A/del的多态性与散发性阿尔茨海默病（SAD）的相关性。方法用常规方法从被试者外周血细胞中提取基因组DNA,通过使用聚合酶链反应-限制性片断长度多态性方法（PCR-RFLP）检测早老素-2基因启动子区域-1560A/del位点的多态性。被试者均来自日本,包括348例SAD患者和年龄、性别相匹配的330例正常对照。观察PSEN2基因启动子区域的多态性分布,用卡方检验和逻辑回归分析进行统计。结果SAD患者组与对照组PSEN2基因的-1560A/del多态性的基因型与等位基因的总体分布无明显统计学意义。（χ^2=1.09,P〉0.05）。结论PSEN2基因启动子区域的-1560A/del多态性可能不是散发性AD发病的风险因素。     

乙酰辅酶A:胆固醇乙酰转移酶基因单核苷酸多态性与散发性阿尔茨海默病的相关性研究

目的 此实验旨在探讨ACAT1的基因甾醇氧-乙酰转移酶（sterol O-acyltransferase． SOAT1）的单核苷酸多态性位点rs1044925与散发性AD（SAD）是否具有相关性。方法 在中国北方汉族人群中收集了SAD107例．以及性别和年龄与之相匹配的同一地区健康对照者118例．采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测了SOAT1多态性位点rs1044925的基因型以及载脂蛋白E（Apolipoprotein E，APOE）的基因型。结果 rs1044925位点在SAD组的基因型（AA．AC．CC）频率分别为82．2％。16．8％，1．0％，在对照组的基因型频率分别为81．4％．17．8％，0．8％．两组间基因型频率差异无显著性（P=1．000，χ^2=0．030，OR=0．863．95％CI=0．478～1．857）。SAD组等位基因（A．C）频率分别为90．7％、9．3％，对照组等位基因频率分别为90．3％、9．7％，两组间等位基因频率差异亦无显著性（P=1．000．χ^2=0．021，OR=0．885，95％CI=0．508～1．774）。当数据用ApoEε4分层后．rs1044925位点基因型频率和等位基因频率两组间差异仍无显著性（P〉0．05）。结论 研究表明在中国北方汉族人群中ACAT1的基因SOAT1多态性位点rs1044925与SAD无相关性，SOAT1可能不是SAD的遗传易感基因。     

脑出血患者屏氧酶1基因192位Gln-Arg多态性的研究

目的　探讨屏氧酶 1( PON1)基因 192位 Gln- Arg( Q/ R192 )多态性与脑出血关系。方法　应用聚合酶链式反应 -限制性片段长度多态性 ( PCR- RFL P)方法 ,对 30 5例脑出血患者和 339例正常对照者 PON1Q/ R192基因多态性进行研究。结果　在脑出血组中 ,PON1Q/ R192 3种基因型频率分别为 QQ13.1%、QR4 8.2 %、RR38.7%。PON1Q/ R192基因型和等位基因频率分布在脑出血组与对照组之间无显著性差异 ( P>0 .0 5 ) ;各基因型之间血脂水平无显著性差异 ( P>0 .0 5 )。结论　研究未发现 PON1Q/ R192基因多态性与脑出血存在相关关系     

精神分裂症和心境障碍混合家系5-HTR 6基因多态性的关联分析

目的 在中国汉族人群精神分裂症和心境障碍混合家系中探讨五羟色胺6受体（5-HTR6）基因267C／T多态性与精神分裂症、心境障碍的关联性。方法 采用聚合酶链反应一限制性片断长度多态（PCR—RFLP）技术对67例精神病混合家系患者及其父母进行5-HTR6基因267C／T多态性检测,并予以传递不平衡检验（TDT）。结果 患者组与父母组之间,5-HTR6基因267C／T多态性等位基因分布（χ^2=2．70,v=1,P〉0．05）和基因型分布（χ^2=2．97,v=2,P〉0．05）无明显差异,5-HTR6基因267C／T多态性与精神分裂症（χ^2=5．16,P〈0．05）存在关联,但与心境障碍（χ^2=2．17,P〉0．05）无关联。结论 在中国汉族人群中5-HTR6基因或邻近基因可能是精神分裂症易患基因之一,但可能不是心境障碍的易患基因。     

精神分裂症伴发2型糖尿病与色氨酸羟化酶基因多态性关联研究

目的：在中国汉族精神分裂症患者中探讨色氨酸羟化酶（TPH）基因A218C（rs1800532）多态性与2型糖尿病共病的关联性。方法：采用聚合酶链反应-限制性片断长度多态（PCR-RFLP）技术在中国汉族人群中对98例伴发2型糖尿病的精神分裂症患者（伴糖尿病组）及109例单纯精神分裂症患者（不伴糖尿病组）进行TPH基因A218C的分型,并进行等位基因及基因型比较。结果：伴糖尿病组与不伴糖尿病组比较,TPH6基因A218C多态性等位基因分布（χ^2=0．00,df=1,P〉0．05）和基因型分布（χ^2=3．78,df=2,P〉0．05）均无显著差异。在男性患者中,伴糖尿病组与不伴糖尿病组基因型分布存在显著差异（χ^2=6．57,df=2,P=0．037）,而等位基因分布（χ^2=1．28,df=1,P=0．26）则无明显差异;在女性患者组中,伴糖尿病组与不伴糖尿病组基因型分布（χ^2=1．54,df=2,P=0．46）和等位基因分布（χ^2=0．02,df=1,P〉0．05）均无显著差异。结论：在中国汉族男性精神分裂症患者中TPH基因A218C多态性与患2型糖尿病存在关联,其可能是男性精神分裂症患者患2型糖尿病的易感基因。     

精神分裂症患者一级亲属的探索性眼球运动与eNOS基因G894T多态性研究

目的：探讨内皮型一氧化氮合成酶（eNOS）基因G894T多态性与精神分裂症患者一级亲属探索性眼球运动（EEM）缺陷的相关性。方法：共收集精神分裂症患者一级亲属193名,正常对照家系一级亲属150名,进行EEM检查,并采用基因芯片技术进行eNOS基因型检测。结果：精神分裂症一级亲属EEM异常率（52%）显著高于正常对照家系一级亲属EEM异常率（15%）（χ^2=52,P〈0.01）;EEM异常者与EEM正常者eNOS基因GT＋TT基因型频率及T等位基因频率差异无显著性（χ^2=2.08,P〉0.05;χ^2=2.55,P〉0.05）。在101名精神分裂症一级亲属的EEM异常者中,对30名GT＋TT基因型携带者与71名GG基因型携带者的凝视点数（NEF）、反应性探索评分（RSS）比较,差异均无显著性（P均〉0.05）。结论：eNOS基因G894T多态性与精神分裂症患者一级亲属的EEM缺陷可能无关。     

对氧磷酶基因与阿尔茨海默病发病风险的Meta分析

目的使用系统评价方法评估对氧磷酶(paraoxonase,PON)基因与阿尔茨海默病(Alzheimer's disease,AD)发病的相关性。方法检索中英文数据库以发现合格研究,使用纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)评价纳入研究质量,采用随机或固定效应模型计算合并比值比(odds ratio,OR),使用Q检验评估研究之间的异质性,失安全系数、Egger's检验和漏斗图评估发表偏倚。结果总共15项研究符合Meta分析纳入标准。所有研究NOS评分均为7分以上,纳入研究质量较高。共涉及4个位点,最多一个位点(PON1Q192R)涉及11项研究,累计病例2366例和对照2579例。结果显示,PON2 S311C多态性SS基因型降低了总人群AD发病风险(OR=0.82,95%CI:0.68~0.99,P=0.04)。没有发现其它遗传多态性与AD具有相关性。结论现有证据表明,PON2 S311C多态性与AD发病风险具有相关性,本结论亟待大样本重复研究进一步验证。     

屏氧酶-1基因多态性和脑梗死的相关性研究

目的 探讨屏氧酶-1（PON-1）基因192位Gin—Arg（Q／R192）多态性与脑梗死的关系。方法 采用聚合酶链式反应（PCR）-限制件片段长度多态性方法测定375例脑梗死患者（脑梗死组）和339名健康普查者及非心脑血管疾病患者（对照组）的PON-1 Q／R192基因多态性,进行基因型分析;并对各基因型与血脂水平关系进行比较。结果 在研究的总人群中,PON-1 Q／R1923种基冈型频率分别为QQ13．6％、QR44．0％、RR42．4％;PON-1 Q／R192皋因型和等位基因频率分布在脑梗死组与对照组之间差异无显著性（P〉0．05）;各基因型之间血脂水：乎差异无显著性（P〉0．05）。结论 未发现PON-1 Q／R192基因多态性与脑梗死存在相关关系。     

对氧磷酶1基因Gln192Arg多态性与帕金森病的相关性

目的探讨中国汉族人群中对氧磷酶1(PON1)基因Gln192Arg单核苷酸多态性(SNP)与帕金森病(PD)的关系。方法采用等位基因特异性聚合酶链反应(A-S PCR)技术检测186例PD患者和228名健康对照PON1基因Gln192Arg位点SNP的分布,分析各基因型与患者发病年龄和疾病严重程度的关系。结果 PD组和对照组间基因型频率和等位基因频率比较差异均无统计学意义(χ2=0.56,P=0.76;χ2=0.06,P=0.81)。进一步按性别分层分析,两组相同性别间基因型和等位基因频率比较亦未发现有统计学差异存在(P>0.05)。PD患者各基因型与发病年龄和疾病严重程度亦无相关性。结论中国汉族人群中PON1基因Gln192Arg位点SNP与PD无相关性。     

Ⅱ型糖尿病并脑梗死患者付氧酶1基因多态性的初步研究

目的 探讨付氧酶1（PON1）A191B基因多态性与单纯Ⅱ型糖尿病及Ⅱ型糖尿病合并脑梗死（CI）的关系。方法 应用聚合酶链式反应（PCR）法，检测72名正常人（对照组）、42例单纯Ⅱ型糖尿病、45例Ⅱ型糖尿病并CI患者PON1 A191B基因型。结果 对照组PON1 191基因B多态性频率与单纯Ⅱ型糖尿病患者（0．63）没有相关关系；而与Ⅱ型糖尿病并CI患者（0．78）显著相关（P＜0．05）。结论 糖尿病并CI患者PON1 191B基因频率明显增高，B基因突变可能是Ⅱ型糖尿病并发CI的危险因素之一。     

Paraoxonase 2 gene C311S polymorphism is associated with a risk of large vessel disease stroke in a Polish population

BACKGROUND: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. METHODS: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. RESULTS: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006-2.48) analyses. CONCLUSION: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.     

Possible association between Cys311Ser polymorphism of paraoxonase 2 gene and late-onset Alzheimer's disease in Chinese

The common polymorphism at codon 311 (C311S) of paraoxonase 2 gene (PON2) was investigated in 165 patients with sporadic late-onset Alzheimer's disease (LOAD) and 174 controls in Chinese. The PON2*C allele frequency was significantly increased in the patients as compared with controls. However, no significant difference was observed after stratification of apolipoprotein E (ApoE) epsilon4 allele. These results suggested that the PON2 polymorphism might be a risk factor for LOAD independent of ApoE epsilon4 status in Chinese.     

Pin基因启动子-842G/C位点多态性与散发性阿尔茨海默病的关联分析

目的:探讨Pin1基因-842G/C位点多态性与散发性阿尔茨海默病(SAD)遗传易感性的关系。方法:应用聚合酶链反应限制性片段长度多态性(PCR-RELP)方法检测46例SAD患者和52名健康老年人的Pin1基因启动子多态性分布特征,并通过比值比(OR)分析基因与SAD之间的关系。结果:Pin1基因启动子多态性(842G/C)与SAD的发病风险不相关,C等位基因与G等位基因的OR=0.90(95%CI=0.37～2.19),而GG基因型与非GG型基因频率在SAD组与健康对照组比较差异无统计学意义(P>0.05)。结论:Pin1基因启动子-842G/C位点多态性可能并不是SAD发病的独立遗传危险因素,与SAD的发病无关。     

Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population

OBJECTIVES: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population. METHODS: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software. RESULTS: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed. DISCUSSION: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.     

Human serum paraoxonase gene polymorphisms,Q192R and L55M,are not associated with the risk of cerebral infarction in Chinese Han population

Abstract

Objectives: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population.

Methods: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software.

Results: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed.

Discussion: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.     

屏氧酶1基因多态性与脑梗死关系研究

目的:探讨屏氧酶1(PONl)A/B192基因型与脑梗死及脑梗死类型的关系。方法:急性脑梗死病人共131例,对照组非心脑血管病人群339例。采用改良的聚合酶链式反应(限制性片段长度多态性方法进行PONIA/B192基因型测定,比较各基因型的分布。结果:动脉粥样硬化血栓性脑梗死的基因型分布与对照组有差异,BB型(58%)明显高于对照组(40%),并且有统计学意义(P<0.05)。结论:PONI192BB型可能与动脉粥样硬化血栓性脑梗死的发生相关。     

BDNF基因启动子区多态性与散发性阿尔茨海默病的相关性研究

目的研究脑源性神经营养因子(BDNF)基因启动子区单核苷酸多态性与散发性阿尔茨海默病(SAD)发病的相关性。方法随机选取10例正常对照组及10例SAD患者进行BDNF基因启动子区-1～-2812bp测序,针对所发现的启动子区单核苷酸多态性(SNP),利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法对328例正常对照者及292例SAD患者进行基因型检测后进行病例-对照关联分析。结果在中国北方汉族人群的BDNF基因启动子区发现1个SNP:-2467G/A(rs908867)。其等位基因及基因型分布在两组间无显著性差异(P值分别为0.10和0.27),经APOEε4分层后它们的分布在两组间也无显著性差异(P>0.05)。结论中国北方汉族人群BDNF基因启动子区的遗传变异可能与SAD发病无关。