Klotho基因3个SNP位点与老年高血压及脂代谢的相关性

目的研究重庆地区汉族人群Klotho基因3个单核苷酸多态性位点的分布规律及其与老年高血压、脂代谢的相关性。方法选择高血压人692例及正常健康人460例作为对照组,提取外周血白细胞基因组DNA,应用单一等位基因特异性引物PCR技术(SASP-PCR)检测Klotho基因3个SNP位点的基因型,同时测定血脂等指标。结果高血压组Klotho基因G-395A SNP AA等位基因频率较对照组增高(P=0.049),GG等位基因频率较对照组低(P0.01);高血压组男性患者AA等位基因型频率较对照组明显增高(P0.01),GG等位基因频率较对照组明显低(P=0.01)。高血压组K lotho基因F352V SNP FF等位基因频率较对照组低(P=0.03),FV等位基因频率与对照组无差异(P=0.057);按性别分层研究,高血压组各等位基因型频率与对照组均无差异(P0.05)。高血压组K lotho基因SNP C370S CC、CS及SS等位基因型频率及性别分层的基因频率与对照组均无显著差异(P0.05)。K lotho基因G-395A SNPGG等位基因携带者其血浆HDL值较GA等位基因增高(P=0.043);Klotho基因F352VSNP FV等位基因携带者其TC值较FF等位基因者低(P=0.01),LDL值也较FF等位基因携带者低(P=0.04),且其HDL值较VV等位基因者增高(P=0.024);Klotho基因C370S SNP各基因型携带者之间其血脂各指标水平无显著性差异(P0.05)。结论 Klotho基因G-395A SNP与老年高血压及血脂有相关性;Klotho基因F352V SNP与高血压及血脂也有相关性;而并未发现Klotho基因C370SSNP与老年高血压及血脂的相关性。     

Klotho基因G-395A多态性与华中地区老年汉族人群颈动脉内中膜厚度的相关性

目的探讨Klotho基因G-395A位点多态性与华中地区老年(年龄≥60岁)汉族人群颈动脉内中膜厚度(IMT)的相关性。方法随机选取278例华中地区老年汉族患者,根据IMT分为IMT增厚组(IMT≥1 mm,132例)和对照组(IMT1 mm,146例),分别检测各组血压、血糖、血脂等生化指标,并用Taq Man基因探针法检测各组Klotho基因G-395A位点的基因型。结果与对照组相比,IMT增厚组GG基因型和G等位基因频率明显增高,AA基因型和A等位基因频率明显降低,AG基因型无明显差异。经多元Logistic回归分析后,G等位基因频率与IMT增厚存在相关性,为IMT增厚的独立危险因子。结论 Klotho基因G-395A位点多态性与华中地区老年汉族人群颈动脉IMT具有相关性,G-395A多态性有可能作为颈动脉IMT增厚的预测指标之一。     

Klotho基因G-395A多态性与动脉硬化的相关性研究

目的研究重庆市汉族人群Klotho基因启动子区域G-395A单核苷酸多态性的分布,探讨该多态性位点与动脉硬化的相关性。方法232例健康体检者均进行臂踝脉搏波传导速度测定,并记录动脉硬化的传统危险因素,根据测定结果分为动脉硬化组(130例)和对照组(102例)。应用TaqMan探针等位基因特异性杂交分析法对Klotho基因G-395A多态性位点进行分析。结果G-395A多态性位点共检测出GG、GA、AA3种基因型,频率分别为60.3%、34.1%和5.6%,符合Hardy-Weinberg平衡。动脉硬化组-395A等位基因的频率显著低于对照组(33.1%vs48.0%,P=0.022)。logistic回归分析,调整传统危险因素后-395A与动脉硬化呈负相关(P=0.042,OR=0.537,95%CI:0.295~0.977)。结论Klotho基因-395A等位基因可能是动脉硬化的遗传学保护因素。     

老年高血压患者klotho基因多态性与其心肾靶器官损害的相关性

目的通过研究老年高血压人群klotho G-395A、F352V、C370S三个位点单核苷酸多态性(SNP)及其等位基因分布特征,揭示klotho基因SNP与其靶器官损害的相关性。方法随机选取符合诊断标准的老年高血压患者391例,应用单一等位基因特异性引物PCR技术检测klotho G-395A、F352V、C370S 3个SNP位点的基因型,研究其与心、肾靶器官损害的相关性。结果高血压并发冠心病组klotho基因G-395A SNP GG、GA及AA等位基因频率与未并发冠心病组均无统计学差异(P0.05);按性别分层,高血压并发冠心病男性亚组AA等位基因频率较无并发冠心病组高(P0.05)。高血压并发冠心病组klotho基因F352V SNP中FV等位基因频率较未并发冠心病组低(P0.05);按性别分层,高血压并发冠心病男性亚组FV等位基因频率较未并发冠心病组低(P0.05)。高血压并发冠心病组klotho基因SNPC 370S CC、CS、SS等位基因频率与未并发冠心病组比较均无统计学差异(P0.05);按性别分层,男性或女性亚组等位基因型频率与未并发冠心病组相比无统计学差异(P0.05)。高血压并发肾损害组与未并发肾损害组相比,klotho基因G-395A、F352V和C370S SNP等位基因频率均无统计学差异(P0.05);按性别分层研究,高血压并发肾损害男性与女性亚组里上述各位点等位基因频率与未并发肾损害组相比无统计学意义(P0.05)。结论携带klotho基因G-395A SNP AA等位基因的男性高血压患者易并发冠心病,而携带有klotho基因SNP F352V FV等位基因的男性高血压患者不易并发冠心病。尚未发现klotho基因G-395A、F352V和C370S SNP与高血压并发肾脏靶器官损害有相关性。     

老年非瓣膜性心房颤动患者血清Ⅰ型及Ⅲ型前胶原肽及血管紧张素转换酶基因多态性

目的探讨心肌纤维化与老年非瓣膜性心房颤动(简称房颤)的相关性及血管紧张素转换酶(ACE)基因插入/缺失多态性与心肌纤维化的关系。方法50例老年房颤患者及43例非房颤患者。用酶联免疫反应(ELISA)法测定心肌纤维化的指标Ⅰ型前胶原羧基端肽(PⅠP)、Ⅲ型前胶原氨基端肽(PⅢP)。用聚合酶链式反应(PCR)的方法检测ACE基因插入(I)/缺失(D)多态性、并比较不同基因型、不同等位基因的分布及其与PⅠP和PⅢP的关系。结果房颤组血清PⅠP、PⅢP水平均显著高于对照组(P<0.05)。其中房颤合并左室肥厚(LVH)较不合并LVH组PⅠP、PⅢP增高(P<0.05)。房颤合并左房扩大较不合并左房扩大组PⅠP、PⅢP高,但尚无统计学差异(P>0.05)。房颤组与对照组ACEI/D多态性缺失纯合型(DD型)、杂合子(DI型)、插入纯合型(Ⅱ型)基因型频率分别为32%,42%,26%和18.6%,42.2%,37.2%;D等位基因分布频率房颤组较对照组高(P<0.05);DD基因型PⅠP、PⅢP浓度高于DI型和Ⅱ型(P<0.05)。结论老年非瓣膜性房颤患者心肌纤维化指标显著升高;并与房颤伴LVH及左房扩大有关;ACEDD基因型可能是心肌纤维化及心脏重构的危险因素。     

慢性阻塞性肺病TNFA和LTA基因等位基因变异分析

目的中国北方汉族人群中研究TNF超家族基因等位基因变异是否与慢性阻塞性肺病(COPD)相关联.方法 以50例COPD患者为研究对象,应用聚合酶链反应-限制性片段长度多态性方法研究TNF超家族基因(TNFA和LTA)等位基因变异分布.结果 TNFA基因多态性位点-308G/A COPD组和对照组比较AA基因型频率分布差异显著(χ2=7.111,P＜0.01),OR值为10.756(95%CI为9.875～12.640).-308G/A多态性位点A等位基因频率差异显著(χ2=8.219,P＜0.01);LTA基因 252A/G多态性位点AG基因型频率分布COPD组与对照组比较差异显著(χ2=11.974,P＜0.01),OR值为4.373(95%CI为3.301～6.872).LTA基因 252 A/G多态性位点G等位基因频率差异不显著.在COPD患者组中TNFA基因GG正常基因型和LTA基因AG杂合基因型结合个体频率比对照组显著增高(χ2=4.10,P＜0.05).结论 中国北方汉族人群LTA基因等位基因变异、TNFA基因多态性变异组合与COPD相关联.     

心房颤动患者衰老基因的表达及其与心肌纤维化的相关性

目的探讨心房颤动(简称房颤)患者KLOTHO基因的表达及其与纤维化的相关性。方法 60例行心脏手术患者按心脏节律分为窦性心律组、阵发性房颤组及持续性房颤动,每组20例。采用用实时荧光定量聚合酶链式反应的方法研究KLOTHO基因mRNA在患者心房肌组织中的表达,及其与血清中心肌纤维化指标Ⅰ型前胶原羧基端肽(PⅠCP)、Ⅲ型前胶原氨基端肽(PⅢNP)的关系。并行心肌组织切片HE染色来观察心肌纤维化的程度。结果①与窦性心律组相比,房颤组左房明显扩大(P0.05),持续性房颤组的左房内径大于阵发性房颤组(P0.05)。②与窦性心律组相比,阵发性房颤、持续性房颤组心房组织的KLOTHO mRNA水平均明显减少(P0.05);持续性房颤组KLOTHO mRNA表达较阵发性房颤组亦明显减少(P0.01)。③窦性心律组心肌间质中仅见极少量胶原纤维;阵发性房颤组心肌间质中胶原沉积增多,心肌肌束周围可见明显胶原纤维包绕;持续性房颤组心肌间质中纤维组织显著增生,心肌肌束被大量的条索状胶原纤维所分隔。④与窦性心律组相比,房颤组血清PⅠCP、PⅢNP含量明显增高(P0.01),且持续性房颤组PⅠCP、PⅢNP含量较阵发性房颤组明显增加(P0.05);⑤房颤患者心肌KLOTHO mRNA水平与左房内径、血清中PⅠCP、PⅢNP呈独立的、显著的负相关关系(P0.01)。结论房颤患者KLOTHO基因的表达增加,心肌纤维化的程度减少,提示KLOTHO基因可能与心房纤维化有关。     

TBX5基因rs3825214位点多态性和心房颤动的相关性

目的探讨TBX5基因多态性与心房颤动的相关性。方法房颤患者100例(房颤组)和非房颤患者(对照组)107例进行TBX5基因rs3825214单核苷酸多态性和房颤的关联研究。所有患者均采集外周血提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)检查患者TBX5基因rs3825214多态性的基因型和等位基因分布。结果 TBX5基因rs3825214位点在入选人群中存在多态性,分别为GG、AG和AA型,其基因型频率在房颤组和对照组分别依次为28.0%,60.0%,12.0%和15.9%,50.5%,33.6%。GG基因型在房颤组的频率分布显著高于对照组(P=0.035),AA基因型在房颤组的频率分布明显低于对照组(P<0.001)。G和A等位基因频率在房颤组和对照组分别为56.0%,44.0%和41.1%,48.9%,G和A等位基因频率在两组间的差异有统计学意义(P=0.001)。结论 TBX5基因rs3825214位点多态性与房颤的发生有相关性,G等位基因可能是房颤的易感基因,GG基因型可能增加了房颤发生的危险性。     

Klotho基因多态性与高血压左室肥厚的关系

目的 探讨klotho基因G395A多态性与高血压左室肥厚的关系.方法 原发性高血压患者76例,为单纯高血压组(A组),高血压左室肥厚组82例(B组),对照组69例(C组).采用聚合酶链反应(PCR)及基因芯片技术检测各组人群的G395A位点基因多态性.结果 Klotho基因G395A多态性GG、GA、AA在三组的分布频率有显著差异(x2=16.976,P＜0.05).单纯高血压组A等位基因频率高于对照组(36.85％ vs 26.09％,P＜0.05).高血压左室肥厚组各基因型分布频率与对照组相比差异有统计学意义(x2=14.307,P＜0.05),A等位基因频率高于对照组(47.56％ vs 26.09％,P＜0.05).结论 高血压左室肥厚组AA基因型频率增加,提示klotho基因G395A多态性可能与高血压及左室肥厚的发生有关.     

细胞毒T淋巴细胞抗原4基因多态性与肝癌易感性的相关性

目的探讨细胞毒T淋巴细胞抗原4(CTLA-4)基因多态性与肝癌易感性的相关性。方法选择陕西省安康市中心医院2016年1月-2018年12月收治的70例肝癌患者,另以70例健康体检者作为对照。所有患者均检测CTLA-4基因外显子49位点的基因型分布。比较2组AA、AG、GG基因型分布与等位基因A、G的基因频率。采用Spearman相关性分析基因型分布与肝癌易感性之间的相关性,并进一步进行基因频率相对风险分析。结果 2组AA、AG、GG基因型的分布存在显著差异,肝癌患者均GG基因型居多,对照组以AG基因型居多(P0.001)。肝癌组G等位基因频率为71.43%,显著高于对照组51.43%(P0.05)。CTLA-4基因多态性与肝癌易感性之间存在明显相关性(r=0.701,P=0.012),携带G等位基因会增加肝癌患病风险[OR=4.101(2.227～10.031)]。结论 CTLA-4基因的外显子49位点基因多态性与肝癌易感性存在较大相关性,携带G等位基因的肝癌患病风险相对更大。     

The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease

The Klotho knockout mouse is thought to be a good animal model for human aging. Recent studies have reported on the association of KLOTHO gene mutation with cardiovascular disease in humans. We observed the frequencies of single nucleotide polymorphisms, that is, G-395A in the promoter region, C1818T in exon 4, and a functional variant, KL-VS, of KLOTHO gene in Koreans, and we investigated their relationships with the presence of coronary artery disease (CAD) in patients who had undergone coronary angiograms. A total of 274 subjects who underwent coronary angiograms because of chest pain were enrolled, and their blood pressure, body mass index, fasting blood glucose level, and lipid profiles were measured. Genotypings were performed on samples of their blood with real-time polymerase chain reaction. Two single nucleotide polymorphisms, G-395A and C1818T, complied with Hardy-Weinberg equilibrium. For the KL-VS genotype, 1 homozygote subject for the adverse allele was detected among the entire population (GG for F352V and CC for C370S). When the subjects were classified into 4 groups according to the number of stenotic vessels, there were no differences among the mean values of the cardiovascular risk factors, except for age and the fasting blood glucose levels, which showed a significant difference between that of the normal and the diseased vessel groups. There were no differences in the prevalence of CAD according to the genotypes of the G-395A polymorphism; however, for the C1818T polymorphism, those subjects with the T allele showed a lower prevalence of CAD than those with the CC genotype. When the subjects were divided into 2 groups according to age, in the group younger than 60 years, T allele carriers of the C1818T polymorphism showed a lower prevalence of CAD than did the noncarriers. In the group older than 60 years, A allele carriers of the G-395A polymorphism showed a lower prevalence of CAD than did the noncarriers. On the haplotype analysis, the GG-CC haplotype showed an increased risk for CAD with an odds ratio of 2.594 (95% confidence interval, 1.385-4.858; P = 0.003). Differential effects of age were observed in the association of KLOTHO G-395A and C1818T polymorphisms with CAD in Koreans. The KL-VS variant seems to be rarely found in the Korean population. These results infer the possibility of the KLOTHO gene being a candidate gene of atherosclerosis in humans, and further research on this topic needs to be done.     

血管紧张素原基因启动子区域单核苷酸多态性与心肌梗死的相关性

为研究血管紧张素原基因启动子区域 - 2 17、- 2 0位和 - 6位上的三种单核苷酸多态性与心肌梗死的相关性 ,采用多重SnaPshot反应 ,在中国南方汉人群中 ,对 2 16例心肌梗死患者和 185名健康对照者进行G 2 17A ,A 2 0C和G 6A多态基因分型。结果发现 ,G 2 17A多态AA、AG和GG基因型分布和A、G等位基因频率在心肌梗死组与对照组之间相比有显著性差异 (分别为 10、77、12 9比 8、37、14 0 ,P =0 .0 0 2 ;2 2 .4 5 %、77.5 5 %比 14 .32 %、85 .6 8% ,P=0 .0 0 3)。G 6A多态AA、AG和GG基因型分布在心肌梗死组和对照组之间亦有显著性差异 (分别为 14 7、6 4、5比12 7、4 4、14 ,P =0 .0 2 9) ,但A、G等位基因频率在两组间无显著性差异 (P =0 .394 )。A 2 0C多态CC、AC和AA基因型分布在两组间有差异 (分别为 6、5 1、15 9比 2、6 1、12 2 ) ,但无统计学意义 (P =0 .0 6 7) ,C、A等位基因频率在两组间亦无显著性差异 (P >0 .0 5 )。Logistic回归分析发现 ,年龄 (P =0 .0 0 1)、收缩压 (P =0 .0 13)和血浆甘油三酯浓度 (P =0 .0 10 )是该人群发生心肌梗死的独立危险因素 ,而高密度脂蛋白胆固醇 (P =0 .0 18)是一种保护因素。结果提示 ,在中国南方汉人群中 ,血管紧张素原基因G 2 17A和G 6A多态可能与心肌梗死的发生     

Relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women

BACKGROUND: Recently, klotho has been proposed as a link between cardiovascular diseases and premature aging, but the relationship between KLOTHO genes and cardiovascular risk factors, especially glucose metabolism, in humans is unclear. OBJECTIVES: We investigate the relationship between polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene with glucose metabolism and cardiovascular risk factors in Korean women. MATERIAL AND METHODS: In 251 women (mean age 51.3+/-6.9 yr), body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, insulin and lipid profiles were measured. The genotyping of polymorphisms G395A in promoter and C1818T in exon 4 of the KLOTHO gene was performed by allelic discrimination using a 5' nuclease polymerase chain reaction assay. RESULTS: Allele frequencies of G395A polymorphism was 0.829 for the G allele and 0.171 for the A allele and allele frequencies of C1818T polymorphism were 0.804 for the C allele and 0.196 for the T allele, both of which were in compliance with Hardy-Weinberg equilibrium and the two polymorphisms were in linkage disequilibrium (D'=0.43, p<0.01). Mean systolic blood pressure was significantly higher in A allele carriers of G395A polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Mean fasting plasma glucose was significantly higher in T allele carriers of C1818T polymorphism compared with non-carriers, and the significance was persistent even after adjustment for age and BMI. Subjects without any minor allele from either single nucleotide polymorphisms (SNP) had significantly lower mean values for systolic, diastolic blood pressure and fasting plasma glucose levels compared with subjects with both minor allele from either SNP. CONCLUSIONS: We observed that KLOTHO G395A polymorphism was associated with blood pressure and KLOTHO C1818T polymorphism was associated with glucose metabolism in Korean women. Further studies are needed to clarify this relationship.     

血管紧张素原基因启动子区域单核苷酸多态与高血压并发冠心病的关系

目的　研究在中国南方汉人群中 ,血管紧张素原基因 (angiotensinogen ,AGT)启动子区域 2 17位和 2 0位上的二种单核苷酸多态与高血压病 (EH)并发冠心病的关系。方法　运用多重SNaPshot反应 ,对 2 0 5例EH并发冠心病患者、185例EH患者和 185名健康对照者进行G 2 17A和A 2 0C多态基因分型。结果　G 2 17A多态的基因型分布在EH并发冠心病组 (AA =8、AG =71、GG =12 6 )和对照组 (AA =8、AG =37、GG =14 0 )之间有显著性差异 (P =0 0 0 5 ) ;A、G等位基因频率与对照组相比亦有显著性差异 (A 2 1 2 2 %、G 78 78%比A 14 32 %、G 85 6 8% ,P =0 0 12 ) ;A 2 0C多态的基因型分布 (CC、AC、AA)及C、A等位基因频率在二组间的差异无显著性 (分别为CC =5、AC =4 9、AA =15 1比CC =2、AC =6 1、AA =12 2 ,P =0 0 97;C 14 39%、A 85 6 1%比C 17 5 7%、A 82 4 3% ,P=0 2 2 6 )。在男性EH并发冠心病组中 ,G 2 17A和A 2 0C多态的基因型分布及其等位基因频率与对照组相比均有显著性差异 (G 2 17A :AA =7、AG =5 3、GG =86比AA =6、AG =2 8、GG =97,P =0 0 2 2 ;A 2 2 95 %、G 77 0 5 %比A 15 2 7%、G 84 73% ,P =0 0 2 2。A 2 0C :CC =3、CA =2 7、AA =116比CC =2、CA =4 3、AA =86 ,P =0 0 2 3;C 11 30 %     

Association of polymorphisms in the estrogen receptor alpha gene with body fat distribution

OBJECTIVE: To examine whether polymorphisms of the estrogen receptor (ER) alpha gene are associated with body fat distribution. DESIGN: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T --> C (PvuII) and an A --> G (XbaI), in the first intron of the ERalpha gene. SUBJECTS: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40-79 y). MEASUREMENTS: The ERalpha genotypes (by automated fluorescent allele-specific DNA primer assay system), anthropometric variables, fat mass (FM) and percentage FM (%FM) (by dual-energy X-ray absorptiometry). RESULTS: FM and waist were inversely associated with age (r=-0.630 and -0.504, respectively) in women with the GG genotype. On the other hand, waist circumference of the AA genotype was positively correlated with age (r=0.231). Thus, for middle-aged women (40-59 y) with the AG or GG genotype body mass index (BMI), %FM, FM, waist, hip and waist-to-hip ratio (WHR) were larger than those with the AA genotype. In particular, FM and waist were greater by 20% and 9%, respectively, for the GG genotype, compared to the AA genotype. Alternatively, FM and waist were smaller by 18% and 6%, respectively, in older women with the GG genotype, compared to the AA genotype. No effect was found among the A --> G polymorphisms for men. For both genders, no difference was found in any variables among the TT, TC and CC genotypes with the exception of BMI of older men (60-79 y). CONCLUSION: No association was found between the ERalpha gene polymorphisms and body fat distribution in men. For women, the A --> G polymorphism, in particular the GG genotype, may contribute to the development of upper-body obesity in middle-aged individuals, but may serve to decrease the whole-body and abdominal fat tissue of older individuals.     

血管紧张素转换酶2基因的多态性与冠状动脉粥样硬化性心脏病的关系

目的:探讨血管紧张素转换酶2(ACE2)基因的多态性与皖北汉族人冠状动脉粥样硬化性心脏病(冠心病,CHD)的关系。方法:采用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)的方法,检测120例CHD患者与109例对照人群(排除CHD患者及健康体检者)的ACE2基因,并进行组间对照研究ACE2基因的多态性与CHD的相关性。结果:在男性CHD患者中,G等位基因的频率明显高于对照组(分别为77.6%、60.7%,P0.05);在女性CHD患者中,携带G等位基因的基因型GG型、AG型的分布频率略高于对照组(分别为43.2%、29.5%和32.1%、28.3%),差别无统计学意义。结论:ACE2基因的多态性与皖北男性汉族人群CHD的发病可能存在相关性,携带G等位基因的男性人群发生CHD的危险性相对较大。     

重庆地区汉族老年人群klotho G-395A、F352V与C370S基因多态性及其组合分布

目的 研究重庆地区汉族老年人群klotho G-395A、F352V与C370S 3个位点的单核苷酸多态性(SNP)及其等位基因频率、单倍型组合分布特征.方法 利用单一等位基因特异性引物PCR技术检测klotho G-395A、F352V、C370S的SNP,应用聚类分析其基因多态性特征.结果 klotho G-395A SNP 基因型分布 GG、GA、AA分别为47.66%、42.58%、9.76%,G、A等位基因频率分别为68.95%、31.05%;klotho F352V SNP 基因型分布 FF、FV、VV分别为35.49%、59.09%、5.61%,F、V等位基因频率分别为65.04%、34.96%;klotho C370S SNP 基因型分布CC CS、SS分别为37.30%、58.76%、3.88%,C、S等位基因频率分别为66.68%、33.32%.研究发现了klotho基因在3个位点的SNP前10种组合基因型分布:klotho G-395G+F352V+C370S 253例(16.92%),klotho G-395A+F352V+C370S 241例(16.12%),klotho G-395G+F352V+C370C 152例(10.17%),klotho G-395A+F352V+C370C 131例(8.76%),klotho G-395G+F352F+C370S 126例(8.43%),klotho G-395A+F352F+C370C 121例(8.09%),klotho G-395G+F352F+C370C 109例(7.29%),klotho G-395A+F352F+C370C 86例(5.75%),klotho A-395A+F352V+C370S 52例(3.48%),klotho A-395A+F352F+C370C 30例(2.01%),klotho G-395G+V352V+C370S 30例(2.01%).结论 本研究首次揭示了klotho基因的3个位点的SNP基因型组合分布特征,为进一步开展klotho基因及其表达研究提供了线索和依据.     

Klotho gene promoter polymorphism and cognitive impairment

Aim:   To study the association between the klotho gene polymorphism and cognitive impairment in community-living men and women.
Methods:   The subjects consisted of 2234 community-living Japanese men and women aged 40–79 years. The klotho gene promoter polymorphism G- 395 A was identified and cognitive function was assessed using the Japanese Wechsler Adult Intelligence Scales – Revised Short Forms ( JWAIS-R SF) and Mini-Mental State Examination (MMSE). Brain infarction and atrophy were assessed by brain magnetic resonance imaging (MRI). The differences in cognitive function, infarction and atrophy were compared between the GG type and GA/AA type of the klotho gene G- 395 A polymorphism.
Results:   The distribution of the klotho gene G- 395 A polymorphism was GG 1639 (73.4%), GA 539 (24.1%), and AA 56 (2.5%). There was no significant difference in intelligence quotient (IQ) between the GG type and GA/AA type in the subjects aged 40–59 years. However, the IQ level was significantly different in terms of the klotho genotype for subjects aged 60–79 years ( P  = 0.004). The mean and SE of IQ levels of the subjects with the GG type and the GA/AA type at nucleotide −395 were 99.8 ± 0.5 and 102.6 ± 0.8, respectively. There were also significant differences in three subtests of JWAIS-R SF – Information, Similarities, and Picture Completion – for subjects aged 60–79 years. Also, the MMSE score was slightly lower for the GG type than for the GA/AA type ( P  = 0.099). However, there were no differences in the findings of brain MRI.
Conclusion:   There were statistically significant differences in cognitive function for klotho gene promoter polymorphism G- 395 A only in subjects aged 60 or over. This polymorphism may be associated with age-related cognitive impairment.     

冠心病患者对氧磷酯酶1基因多态性分析

目的 :探讨冠心病 (CHD)患者对氧磷酯酶 1(Paraoxonase 1,PON1)基因多态性与血脂的关系及其病因学意义。方法 :使用Taqman特异性等位基因鉴别法检测 93例CHD患者和 138例健康对照者的基因组DNA ,测定该基因G 12 6C、L5 5M和Q192R三个多态性的基因型和由三个位点的等位基因组成的单体型。统计分析两组间这些基因型和单体型频率分布差异性 ,以及不同基因型与血脂水平的相关性。结果 :CHD患者中Q192R位点的QQ基因型携带者明显少于健康对照者 (7.5 %∶18.1% ,P <0 .0 5 ) ,各种单体型在两组间差异无显著性意义。各基因型之间血脂水平差异亦无显著性意义。结论 :PON1基因中只有Q192R多态性与CHD的发病相关