ApoE基因多态性与早发冠心病关系的研究

目的:研究载脂蛋白E(ApoE)基因多态性与早发冠心病CHD)的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)基因分析方法,测定92例早发CHD、237例迟发CHD患者和220名对照者的ApoE基因型;血脂水平按常规方法测定。结果:发现的5种ApoE基因型,分别为E3/3、E2/2、E3/2、E4/3及E4/2。早发CHD组和迟发CHD组ApoE 4/3基因型和ε4等位基因频率均高于对照组(P＜0．01);进一步对两组CHD患者的ApoE多态性进行分析,发现早发组ε4等位基因频率较迟发组高(P＜0．05)。ApoE各等位基因型之间,TC和LDL-C水平之间存在统计学差异(P＜0．05)。结论:ApoE基因多态性与早发CHD的发生发展有关。     

蒙古山羊和哈萨克山羊GOLA-DRB3基因的HaeⅢ酶切多态性分析

采用限制性内切核酸酶HaeⅢ对蒙古山羊和哈萨克山羊GOLA-DRB3基因外显子2的285bp扩增产物进行了PCR-RFLP多态性分析,共检测到17种基因型,由A、B、C、D、E、F和H等7个复等位基因控制;通过酶切图谱分析发现蒙古山羊和哈萨克山羊的GOLA-DRB3基因外显子2的154、168和220位碱基表现出多态性。并对基因型频率和等位基因频率进行了统计分析,结果表明,GOLA-DRB3基因的部分基因型频率和等位基因频率在两个群体之间差异显著（P＜0.10或P＜0.05）或极显著（P＜0.01）; χ2适合性检验结果表明,蒙古山羊和哈萨克山羊的GOLA-DRB3基因外显子2的HaeⅢ酶切位点均未达到Hardy-Weinberg平衡状态（P＜0.01）。 Abstract:The exon2 of GOLA-DRB3 gene was amplified and a uniform fragment of 285bp was obtained in Mongolian Goat and Kazakh Goat.The 285bp PCR product was digested with restriction endomuclease HaeⅢ and genetic polymorphism was investigated by PCR-RFLP.Seventeen kinds of genotypes were found in two populations,which were controlled by seven alleles.There are significant differences in some genotypic frequencies and gene frequencies between the two populations（P＜0.10,P＜0.05,P＜0.01）;The results of χ2 test showed that genotypes of GOLA-DRB3 gene in two populations did not fit with Hardy-Weinberg equilibrium（P＜0.01）.     

载脂蛋白E基因多态性与动脉粥样硬化性脑梗塞关系的研究

应用聚合酶链反应(PCR)扩增ApoE基因外显子4中编码112位和158位氨基酸的 DNA片段,将该长为292bp的PCR产物以HhaI酶切,根据其限制性片段长度多态性图谱确定ApoE基因型。对广东汉族人群的50例动脉粥样硬化脑梗塞(ACI)患者和50例健康对照者的ApoE基因多态性频率的研究结果表明:所研究的人群中,ApoE基因多态性频率与ACI没有关联。ACI患者中各基因型亚组之间血清TG和TC浓度无显著性差异。 Abstract:The polymerase chain reaction(PCR)and restriction fragment length polymorphism techniques(RFLPs)were used to study the relation between apolipoprotein E gene polymorphism and atherosclerotic cerebral infarction(ACI).A 292 bp DNA fragment containing codes for the 112 and 158 amino acid residues in the fourth exon of ApoE gene was amplified by PCR.The PCR products were digested with HhaI.The polymorphism patterns of Apo E gene,allele frequencies in 50 Chinese healthy and 50 patients with ACI,and the serum levels of TG and TC in the different subgenotypes of 50 patients with ACI were detected.,no statistical significant differences of alleles frequencies were found between the cases with ACI and the control,and no statistical significant differences of the serum levels of TG and TC were found among the different subgenotypes of 50 patients with ACI.These results suggested that ApoE gene polymorphism was not associated with the development of ACI.     

中国汉蒙两族人群MTHFR基因热敏感性多态性分布的比较

为比较中国蒙汉两族人群MTHFR基因第677位核苷酸多态性的分布情况,获得该位点多态性的群体遗传学数据,本研究应用PCR扩增技术, 其扩增产物用限制性核酸内切酶Hinf I消化后进行非变性聚丙烯酰胺凝胶电泳,分析蒙汉族人群中MTHFR基因第677位核苷酸基因型（野生型、杂合型和突变纯合型）的分布频率。结果表明,蒙族人群基因型构成以野生型为主,占45.6％,突变杂合型占39.2％,突变纯合型仅占15.2％,汉族人群基因型构成以突变杂合型为主,占55.7％,野生型仅占17.9％,突变纯合型占26.4％,明显高于蒙族人群。经χ2检验,两组基因型构成比具有显著性差异（P<0.001）;蒙族人群MTHFR 677T等位基因频率为34.8％,经u检验显著低于汉族人群（54.2％）的频率。据此认为,中国蒙族人群MTHFR热敏感性基因突变频率显著低于汉族人群,提示该基因多态性分布在中国不同民族人群中存在差异。 Abstract：The purpose of this study is to compare the genetic polymorphism distribution of the 677th nucleotide of MTHFR between the Mongolian population and the Hans of China,and to obtain the population genetic data of this polymorphism.Using PCR－RFLP method,the authors analyzed the genotypes of the 677th nucleotide of MTHFR in Mongolians and Hans.Results show that in Mongolian population,the proportion of wild type is 45.6％,proportion of heterozygotes is 39.2％ and that of homozygotes is 15.2％; While in Hans,proportions are wild type 17.9％,heterozygotes 55.7％ and homozygotes 26.4％.The ratios of genotypes are significantly different between Mongolian and Han populations(χ2－test,P<0.001).The 677th allele frequency in Mongolians is 34.8％,lower than that in Hans(54.2％,u－test,P<0.001).This suggests that the mutant MTHFR gene frequency is significantly higher in the Han population than in the Mongolian population in China.     

中国广东汉族人群核苷酸修复基因hMTH1 遗传多态性研究

为研究中国南方汉族人群核苷酸修复基因hMTH1遗传多态性,应用聚合酶链反应-单链构象多态性技术检测172名健康人外周血白细胞hMTH1基因启动子及全部5个外显子多态性,并进行DNA测序。结果发现hMTH1基因启动子及外显子1序列保守,未见突变;外显子2第73位碱基存在T→C杂合型突变,基因型TT和TC频率分别为93.02%、6.98%,等位基因T和C频率分别为96.51%、3.49％;外显子3第45位遗传密码存在T→C杂合型突变,基因型TT和TC频率分别为95.35%、4.65%,等位基因T和C频率分别为97.67%、2.33%,该多态性为首次发现;外显子4第83位遗传密码存在G→A杂合型突变,基因型GG和GA频率分别为89.53%、10.47%,等位基因G和A频率分别为94.77%、5.23％;外显子5第119位氨基酸遗传密码存在C→T杂合型突变,基因型CC和CT频率分别为95.93%、4.07%,等位基因C和T频率分别为97.97%、2.03％。Abstract: In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene’s promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49％, respectively. A T to C polymorphism was detected at codon 45 in exon3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23％, respectively. A C to T polymorphism was detected at codon 119 in exon5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03％, respectively.     

上海地区汉族人5-HT2a受体基因T102C多态性的基因频率分布

为了揭示中国汉族人5-HT2a受体基因T102C多态性基因频率的分布,我们随机抽取了226例汉族健康人作研究,用限制性片段长度多态性(RFLPs)技术测定研究对象的基因型和等位基因。结果发现汉族正常人5-HT2a受体基因T102C多态性基因型频率依次为:A1/A2=0.5044,A1/A1=0.2965,A2/A2 =0.1991,两种等位基因频率依次为:A1=0.5487,A2=0.4513,杂合度H=0.50 44、期望杂合度h=0.4953,多态信息量PIC=0.3726,表明T102C多态性具有合适信息,对疾病的关联研究,法医学鉴定有一定的价值。 Abstract:To investigate the distribution about genotype and allele frequencies of T102C polymorphism in the 5-HT2a receptor gene Chinese Han population,the genotypes and alleles of 226 healthy person were examined with Restriction Fragment Length Polymorphisms(RFLPs)technique.The genotype frequencies are as follows:A1/A2=0.5044,A1/A1=0.2965,A2/A2=0.1991,respectively,and the allele frequencies are as follows:A1=0.5487,A2=0.4513,respectively.The heterozygosity(H)is 0.5044,the expected heterozygosity(h)is 0.4953,and the Polymorphism Information Content(PIC)is 0.3726.Our findings suggest that the T102C polymorphism in 5-HT2a receptor gene may have suitable information to be used for association study or forensic identification.     

飞行员中血管紧张素转换酶基因插入或缺失多态性研究

为了解飞行员血管紧张素转换酶(ACE)基因插入或缺失（I/D）多态性情况,探讨ACE基因多态性与飞行员耐力可能的关系,用聚合酶链反应（PCR）扩增技术检测118例飞行员和96例健康对照者的ACE基因I/D多态性。 结果位于ACE基因内含子16的I/D多态性经PCR扩增后呈三种基因型：纯合子插入型（II）、纯合子缺失型（DD）和杂合子插入或缺失型（I/D）。飞行员组II基因型（44.07%）和I等位基因频率（0.65）显著高于健康对照组(分别为31.25%和0.52)。 结果表明ACE I基因有可能在飞行员的飞行耐力中起重要作用。 Abstract:In order to understand insertion/delation (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in pilots,and to explore the relationship between ACE gene I/D polymorphism and the perfomance of the pilots,the polymerase chain reaction (PCR) was used to determine the genotypes for an I/D polymorphism in intron 16 of the ACE gene in 118 pilots and 96 healthy subjects as controls.The result showed that the I/D polymorphism in intron 16 of the ACE gene was categorized into three genotypes: two deletion alleles (genotype DD),heterozygous alleles (genotype ID),and two insertion alleles (genotype II).The genotype II and I allele frequency were significantly higher in pilots (44.07% and 0.65) than that in healthy subjects (31.25% and 0.52).It is suggested that I gene of ACE may play a role in perfomance of the pilots.     

磺酰脲类受体基因多态性与2型糖尿病的相关性研究

研 究磺酰脲类受体1（SUR1）基因外显子16-3c/t多态性在中国某南方汉族人群中是否为2型糖尿病的致病基因座。采用聚合酶链反应-限制酶酶切片段长度多态性（PCR-RFLP）方法对南方汉族46个2型糖尿病高发家系成员的SUR1基因外显子16的多态性进行分析。利用Mantel-Haenszel分层分析研究该基因座多态性与2型糖尿病的关系。在高发家系人群中,SUR1基因外显子16-3c/t多态性的基因型频率为：cc型29.3%、ct型507%、tt型20%,c等位基因频率为54.7%;患者组基因型频率为：cc型30.2% 、ct型53.8%、tt型16.0% ,c等位基因频率为57.1% ;未患病亲属组基因型频率为：cc型28.3% 、ct型47.2%、tt型24.5%,c等位基因频率为519%,两组间基因型和等位基因的差异经检验无统计学意义（分别为χ2=3.224,P=0.199;χ2=1.250,P=0264）。在性别、吸烟、饮酒、肥胖、高血压等混杂因素中的频率差异亦无显著性。c等位基因频率低于北方汉族人。在中国某南方汉族2型糖尿病高发家族人群中,未发现SUR1基因外显子16-3c/t多态性与2型糖尿病存在关联,该基因座可能不是该人群的致病基因。 Abstract:To study whether the 3c/t polymorphism of the sulfonylurea receptor 1 (SUR1) gene exon16 increased the risk of type 2 diabetes mellitus in type 2 diabetes mellitus pedigrees in Han population in south area of China.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 46 type 2 diabetes mellitus pedigrees.The polymorphism in SUR1 was tested and analyzed by Mantel-Haenszel χ2 test.Frequencies of SUR1-3c/t polymorphism had no significant difference between type 2 diabetes mellitus and normal relatives（genotypes χ2=3.224,P=0.199;frequency of allele χ2=1.250,P=0.264）.In all subjects,type 2 diabetes mellitus and normal relatives,SUR1-3c/t genotypes were listed (cc:29.3%,30.2%,28.3%;ct:50.7%,53.8%,47.2%;tt:20%,16.0%,24.5% respectively).The frequencies of c were 54.7%,57.1% and 51.9% respectively.The frequency of c is lower than Han population in northern China.The results show that SUR1 exon16-3c/t polymorphism is not associated with type 2 diabetes mellitus in the population.     

载脂蛋白E基因多态性与持续性植物状态的关系及其意义

研究载脂蛋白E(ApoE)基因多态性与持续性植物状态 (PVS)之间的关系 ,探讨PVS发生的遗传背景及其对血脂水平的影响。以 6 2名PVS患者为研究对象 ,5 5名正常人为对照 ,采用聚合酶链反应和限制性片段长度多态性(PCR RFLP)方法 ,分析了载脂蛋白E基因多态性 :血脂水平按常规酶法进行测定并进行统计学处理。ApoE基因多态分析表明 ,在PVS患者和正常人中观察到 5种ApoE基因型 ,分别为E3/ 3、E3/ 4、E2 / 2、E2 / 3及E4 / 2。PVS患者组ApoE3/ 4基因型频率高于对照组 (χ2 =14 .2 36 ,P <0 .0 0 1) ;而E3/ 3基因型频率较对照组显著降低 (χ2 =5 .348,P <0 .0 5 )。PVS患者的ε4等位基因频率显著高于对照组 (χ2 =10 .5 33,P <0 .0 0 1) ;而ε3等位基因频率显著低于对照组 (χ2 =7.0 2 2 ,P <0 .0 1)。两组ApoE基因型E2 / 2 ,E2 / 4 ,E2 / 3,E3/ 4的低密度脂蛋白胆固醇 (LDL C)水平之间存在统计学差异 (P <0 .0 5 ,P <0 .0 5 ,P <0 .0 5 ,P <0 .0 1)。ApoE基因多态性与PVS有关联 ,并影响患者的血脂水平。ApoE基因多态性可能与PVS的发生和预后有关     

组织蛋白酶D基因C224T多态与散发阿尔茨海默氏病的关联研究

组织蛋白酶D（Cathepsin D）是一种细胞核内体/溶酶体内的门冬酰胺蛋白酶。它有可能通过剪切淀粉样前体蛋白参与阿尔茨海默氏病（Alzheimer’s disease, AD）相关的神经退化。在以德国人为对象中的研究显示组织蛋白酶D基因（CTSD）C224T多态与AD发病风险紧密相关。然而,此结果未能在另一些群体中得到重复。为此,我们通过聚合酶链反应-限制性片段长度多态性方法分析了CTSD基因C224T多态性和载脂蛋白E（apolipoprotein E, ApoE）基因多态性在成都地区汉族老年人中的分布,探讨了CTSD C224T多态与散发AD的相关性。结果发现CTSD基因C224T多态分布在病例组与对照组之间没有显著性差异,提示成都地区汉族人群中CTSD基因C224T多态与散发AD不具有关联;但比值比的比较提示CTSD等位基因T和ApoEε4有弱的协同作用。Abstract: Cathepsin D is the major lysosomal/endosomal aspartic protease and exhibits β- and γ-secretase-like activity in vitro. Data from German suggest that the C224T polymorphism in the Cathepsin D gene (CTSD) exon 2 is strongly associated with the risk for Alzheimer’s disease (AD).Meanwhile other studies have not been able to replicate the result. It’s necessary to determine the genotype of the polymorphism in CTSD in Chinese sporadic AD patients and age-matched controls with normal cognition and examine possible association of the polymorphism with the disease. We find no strong evidence of association between the CTSD C224T polymorphism and Chinese sporadic AD. Whereas there may be a weak synergistic interaction between ApoE ε4 and CTSD T allele.     

Co-inheritance of specific genotypes of HSPG and ApoE gene increases risk of type 2 diabetic nephropathy

The objective of this paper is to investigate co-inheritance of specific HSPG and ApoE genotypes in the development of Chinese type 2 diabetic nephropathy. PCR-RFLP was used to detect HSPG and ApoE genotypes in 385 Chinese subjects including 298 patients with type 2 diabetes mellitus (T2DM) and 87 non-diabetic controls (Non-DM). The T2DM group was subdivided into patients with (TDN; n = 218) and without diabetic nephropathy (Non-DN; n = 80). The latter group was further subdivided into groups of patients with microalbuminuria nephropathy (DN-1; n = 129) and severe diabetic nephropathy (DN-2; n = 89). We then compared the relative frequencies of various HSPG and ApoE genotypes and alleles among the groups, searching for predictive trends. The T allele of the HSPG gene occurred more frequently in the DN-2 group than in the Non-DN or DN-1 or groups, their (Fisher's exact p was 1.05 × 10^–3 and 6.58 × 10^–6; odds ratios were 2.09 (95% CI 1.32–3.30) and 2.48 (95% CI 1.64–3.74), respectively. The E2 allele of the ApoE gene occurred more frequently in the T2DM than in the Non-DM group, the Fisher's exact p was 0.0087; odds ratio was 3.45 (95% CI 1.30–9.81). Genotype analysis showed that the TT or TG of HSPG gene were paired with the E2/2 or E2/3 of ApoE gene significantly more frequently in the TDN group than in the Non-DN group, with an odds ratio of 3.03 (95% CI 1.03–8.90). There was no significant differences in other combinations of genotypes in HSPG and ApoE genes between TDN and Non-DN group. These results suggest that the HSPG T allele is a risk factor for the development of severe diabetic nephropathy in type 2 diabetic patients, and that the ApoE E2 allele is a risk factor for the occurrence of type 2 diabetes mellitus in Chinese general population. In addition, we find that co-inheritance of T/E2 confers a higher risk of type 2 diabetes mellitus progression to diabetic nephropathy in Chinese.     

Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism

Apolipoprotein E (ApoE) is a major constituent of many lipoprotein particles. Previous genetic studies have focused on six genotypes defined by three alleles, denoted epsilon2, epsilon3, and epsilon4, encoded by two variable exonic sites that segregate in most populations. We have reported studies of the distribution of alleles of 20 biallelic variable sites in the gene encoding the ApoE molecule within and among samples, ascertained without regard to health, from each of three populations: African Americans from Jackson, Miss.; Europeans from North Karelia, Finland; and non-Hispanic European Americans from Rochester, Minn. Here we ask (1) how much variation in blood levels of ApoE (lnApoE), of total cholesterol (TC), of high-density lipoprotein cholesterol (HDL-C), and of triglyceride (lnTG) is statistically explained by variation among APOE genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles; (2) how much additional variation in these traits is explained by genotypes defined by combining the two variable sites that define these three alleles with one or more additional variable sites; and (3) what are the locations and relative allele frequencies of the sites that define multisite genotypes that significantly improve the statistical explanation of variation beyond that provided by the genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles, separately for each of the six gender-population strata. This study establishes that the use of only genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles gives an incomplete picture of the contribution that the variation in the APOE gene makes to the statistical explanation of interindividual variation in blood measurements of lipid metabolism. The addition of variable sites to the genotype definition significantly improved the ability to explain variation in lnApoE and in TC and resulted in the explanation of variation in HDL-C and in lnTG. The combination of additional sites that explained the greatest amount of trait variation was different for different traits and varied among the six gender-population strata. The role that noncoding variable sites play in the explanation of pleiotropic effects on different measures of lipid metabolism reveals that both regulatory and structural functional variation in the APOE gene influences measures of lipid metabolism. This study demonstrates that resequencing of the complete gene in a sample of >/=20 individuals and an evaluation of all combinations of the identified variable sites, separately for each population and interacting environmental context, may be necessary to fully characterize the impact that a gene has on variation in related traits of a metabolic system.     

Apo E gene polymorphism on development of diabetic nephropathy

Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (epsilon2, epsilon3 and epsilon4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The epsilon4 allele frequency was significantly higher in-group I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with epsilon2 alleles than epsilon3 and epsilon4 alleles. In conclusion, the present prospective study indicates that the epsilon4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.     

Association of IL-4 receptor gene polymorphisms with high density lipoprotein cholesterol

The aim of this study is to investigate the correlation between E400A polymorphisms of interleukin-4 receptor α chain (IL-4Rα) and lipid metabolism. Genomic DNA from 121 type 2 diabetes mellitus (T2DM) patients and 113 non-diabetic, non-obese control study subjects were extracted, and their IL-4Rα E400A polymorphisms were analyzed by PCR-RFLP. The correlation between IL-4Rα E400A genotypes and study subjects' lipid profile was then examined. Significant associations of the IL-4Rα E400A genotypes and high density lipoprotein-cholesterol (HDL-C) levels among control individuals (p=0.007), as well as among the T2DM patients (p=0.029), were observed. Significant correlations between IL-4Rα E400A genotypes with blood pressure, as well as with blood urea nitrogen, were also observed in control subjects. Our results reveal that IL-4Rα may play certain roles in the lipid metabolism of Taiwanese population and suggest a novel link between lipid metabolism and the cytokine receptor.     

Is the ApoE polymorphism associated with dilated cardiomyopathy?

Apolipoprotein E (ApoE) is 34 kDa protein involved in the modulation of cholesterol transport and homeostasis. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular and neuronal diseases. ApoE epsilon4 allele has been reported to be associated with increased risk of cardiovascular diseases such as myocardial infarction, hypertension, coronary heart disease, etc. Fifty patients with the end-stage dilated cardiomyopathy (DCM) and advanced congestive heart failure were examined in our study. For evaluation of ApoE polymorphism, novel approach of fast screening of ApoE gene polymorphism by combination of PCR and blotting (CVD StripAssay) was used. Individual genotypes were correlated with basic cardiologic clinical parameters. The reported frequency of this allele in Caucasian population is 14.7 %. Our results showed that in patients with DCM frequency of the ApoE epsilon4 allele is 40 %. Frequency of the genotype epsilon2/4 was 58 % and epsilon3/4 was 22 %. Comparison with control Caucasian groups monitored by others clearly revealed that frequency of epsilon4 alelle is increased in patients with advanced stages of DCM. This observation suggests association of ApoE polymorphism with severe form of DCM. Physiological consequences of this observation remain to be clarified.     

Apolipoprotein E gene polymorphism,hypercholesterolemia and glomerular filtration rate in type 2 diabetic subjects: A 9-year follow-up study

OBJECTIVE: To study the association between apolipoprotein E (apoE) genotype and the rate of decline in glomerular filtration rate (GFR) in type 2 diabetic patients in a 9-year prospective study. METHODS: GFR was determined in 84 type 2 diabetic patients by plasma clearance of (51)Cr-EDTA at baseline and after 9 years of follow-up. ApoE genotypes were determined by polymerase chain reaction and restriction enzyme HHAI digestion and designated as epsilon4 allele group (apoE4/2, 4/3 and 4/4 genotypes; n = 20) and non-epsilon4 allele group (apoE3/3 and E3/2 genotypes; n = 64). We focused our analysis on those patients who were more likely to progress to diabetic renal disease, i.e. whose GFR fell more than expected in the normal course of ageing [1 ml x min(-1) x (1.73 m(2))(-1) per year]. RESULTS: In the whole population, the decline in the GFR did not differ statistically significantly between the apoE genotype groups [p = 0.65 with analysis of variance for repeated variables (RANOVA) for interaction between apoE genotype group and time point]. However, among patients whose GFR changed more than 9 ml x min(-1) x (1.73 m(2))(-1), GFR showed a statistically significantly greater decline in the epsilon4 allele group (n = 11) than in the non-epsilon4 allele group (n = 43) [from 116 +/- 36 to 80 +/- 29 ml x min(-1) x (1.73 m(2))(-1) vs. from 119 +/- 20 to 96 +/- 18 ml x min(-1) x (1.73 m(2))(-1); p = 0.005 with RANOVA]. CONCLUSION: ApoE allele epsilon4 may speed up the rate of decline of the GFR in patients with progressive diabetic renal disease.     

SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4, SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus, T2DM)的关系, 文章采用病例对照设计, 选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象, 应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法, 检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况, 比较T2DM组糖化血红蛋白(Hemoglobin A_1c, HbA_1c)在各基因型间的分布, 并进行单倍型分析。结果显示：①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs. 0.282, P =0.017); GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001; OR, 1.563; 95% CI, 1.189-2.053); 在显性模型(GG+GA vs. AA)分析中, G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P =0.002; OR, 1.525; 95% CI, 1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P >0.05)。②在T2DM组, rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA_1c水平, 但各基因型携带者之间HbA_1c水平并无统计学差异(P >0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1); 而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论：rs237025多态性与北京汉族人群T2DM的易感性相关, rs237024和rs600739多态性可能与T2DM的易感性不相关。     

SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4,SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus,T2DM)的关系,文章采用病例对照设计,选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象,应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法,检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况,比较T2DM组糖化血红蛋白(Hemoglobin A1c,HbA1c)在各基因型间的分布,并进行单倍型分析。结果显示:①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs.0.282,P=0.017);GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001;OR,1.563;95%CI,1.189-2.053);在显性模型(GG+GA vs.AA)分析中,G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P=0.002;OR,1.525;95%CI,1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P>0.05)。②在T2DM组,rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA1c水平,但各基因型携带者之间HbA1c水平并无统计学差异(P>0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1);而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论:rs237025多态性与北京汉族人群T2DM的易感性相关,rs237024和rs600739多态性可能与T2DM的易感性不相关。     

Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults

The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females.     

Apolipoprotein E gene polymorphisms in Lebanese with hypercholesterolemia

Apolipoprotein E (ApoE) has an important role in the metabolism of lipids through its major isoforms (ε2, ε3, ε4). In particular, ApoE ε4, has been considered as a major genetic risk factor for cardiovascular diseases (CVD). The aim of our study is to investigate the frequency of ApoE gene polymorphisms (rs 429358C > T, rs 7412C > T) and their relationship to lipid parameters in a group of Lebanese hypercholesterolemic subjects (22 males and 24 females, aged 25–80 years). Lipid profile, apolipoproteins A-I and B were determined using fasting serum samples; and molecular analysis of ApoE polymorphisms using blood in EDTA tubes. The distribution of the four ApoE genotypes detected in this study was: ε3/ε3 (73.9%), ε3/ε4 (17.4%), ε2/ε3 (6.5%), and ε2/ε4 (2.2%) resulting in allelic frequencies for ε2, ε3 and ε4 of 4.3%, 85.9% and 9.8%, respectively. No association was determined among any of the lipid parameters, gender and ApoE genotypes. Lipid parameters were not statistically different among various ApoE genotypes (p > 0.05). ApoE ε2 frequency was found to be lower than that previously reported for healthy Lebanese (7.2%). CVD is one of the major leading causes of mortality in Lebanon with a reported prevalence of 12.2% in males and 7.7% in females, which incidentally agrees with our finding regarding ε4 allelic frequency of 13.6% in males and 6.3% in females. Consequently, larger prospective studies are recommended to highlight the correlation of ApoE polymorphisms to other biochemical and environmental factors involved in CVD.