间隙性连接蛋白37基因1019C/T多态性与原发性高血压的关系

目的 研究无锡地区人群中间隙性连接蛋白37 （connexin 37,CX 37）基因1019C/T多态性与原发性高血压的相关性.方法 入选在无锡市人民医院初次诊断为原发性高血压的患者1 126例,874名健康体检者作为正常对照组,均采用基因测序技术对CX37基因1019多态性位点基因型进行检测,比较两组人群中基因型及等位基因分布差异.结果 （1）两组人群中均存在CX 37基因1019C/T多态性,基因型分布均符合Hardy-Weinberg遗传平衡定律.（2）原发性高血压组与正常对照组相比,C等位基因分布频率升高（57.37％vs.42.05％,P＜0.01）.C等位基因携带者（CC＋TC）在原发性高血压组高于对照组,差异有统计学意义（80.46％ vs.66.70％,P＜0.01）.与Tr纯合子相比,（CC＋TC）基因型原发性高血压患病风险增加（OR=2.06,95％ CI：1.68～2.52）.对性别进行亚组分析显示：无论男性还是女性人群中原发性高血压组C等位基因携带者频率均显著高于正常对照组（男性：79.19％vs.69.05％,P＜0.01;女性：81.75％ vs.64.40％,P＜0.01）,C等位基因携带者原发性高血压患病风险明显高于TT型（男性：OR=1.71,95％CI：1.28～2.27;女性：OR=2.48,95％ CI：1.85～3.31）.结论 CX37 C等位基因可能与老年原发性高血压相关.     

原发性高血压患者醛固酮合酶基因-344T/C多态性与心房颤动的相关性研究

目的探讨中国河南豫北地区原发性高血压人群醛固酮合酶(CYP11B2)基因一344T/C多态性与心房颤动(房颤)的关系。方法运用病例对照法,选择803例原发性高血压患者,运用PCR-RFLP技术对405例伴房颤者(房颤组)和398例窦性心律者(窦律组)的CYP11B2基因-344T/C多态性进行基因分型,并进行分析。结果 2组T和C等位基因分布,差异无统计学意义(χ~2=1.32,P=0.25);房颤组CC基因频率明显高于窦律组(χ~2=21.29,P<0.05)。与携带TT或TC基因型者比较,携带CC基因型高血压患者患房颤的风险增加(OR=1.96,95%CJ:1.23～2.67),携带CC基因型的高血压合并房颤患者左心房内径明显增高(P<0.05)。结论 CYP11B2基因—344T/C多态性与原发性高血压患者房颤的发生相关。     

恩施土家族人群eNOS rs1799983基因多态性和肥胖在原发性高血压中的交互作用

目的 探讨恩施土家族人群内皮型一氧化氮合酶(eNOS)rs1799983多态性与原发性高血压(EH)关联性及其与肥胖交互作用。方法 采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析127例EH患者和127名正常对照eNOS rs1799983基因型。非条件Logistic分析各基因型与发病中易感性关系以及与肥胖的交互作用。结果 携带C(CC/CT)基因个体患病风险较非C基因携带者(TT)风险明显增加1.35倍(OR=1.35,95%CI: 1.22,2.56,P<0.01;校正OR=1.61,95%CI: 1.21,3.01,P<0.01);非条件Logistic分析表明携带CC/CT基因型肥胖个体EH罹患风险是携带TT基因非肥胖个体的3.39倍(OR=3.39,95%CI:2.66,5.36,P=0.000)(RERI=1.94,95%CI:1.41,2.77;API=0.59,95%CI:0.33,0.84;S=1.46,95%CI:1.37,2.66)。结论 eNOS rs1799983多态性增加恩施土家族个体原发性高血压罹患风险,且与肥胖存在原发性高血压发病中存在协同效应。     

内皮型一氧化氮合酶基因G894T多态性与蒙古族原发性高血压合并卒中的关系

目的探讨内皮型一氧化氮合酶（eNOS）基因G894T多态性与蒙古族原发性高血压及原发性高血压合并卒中之间的关系。方法选择长期生活在内蒙古乌拉特后旗、三代血亲内无其他民族的蒙古族人群286例,其中原发性高血压合并卒中组70例,原发性高血压组104例,正常血压组112名。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）技术检测3组eNOS基因G894T多态性。结果原发性高血压合并卒中组eNOS基因G894T位点GG、GT＋TT基因型频率为75.7%、24.3%,G、T等位基因频率为86.4%、13.6%;原发性高血压基因型频率为81.7%、18.3%,等位基因频率为89.9%、10.1%;正常血压组基因型频率为93.8%、6.2%,等位基因频率为96.9%、3.1%。3组基因型频率及等位基因频率比较,差异均有统计学意义（χ2=12.240,OR=4.811,95%CI：1.879~12.318;χ2=14.175,OR=4.868,95%CI：1.990~11.909;χ2=7.358,OR=3.353,95%CI：1.346~8.351;χ2=8.647,OR=3.481,95%CI：1.448~8.372）,原发性高血压合并卒中组与原发性高血压组比较,差异均无统计学意义（χ2=0.601,OR=1.329,95%CI：0.646~2.734;χ2=0.993,OR=0.398,95%CI：0.720~2.709）。结论eNOS基因G894T多态性的T等位基因与蒙古族人群原发性高血压及原发性高血压合并卒中的发生可能相关。     

脑利钠肽T-381C基因多态性与高血压的关系

目的探讨脑利钠肽T-381C基因多态性与高血压的关系。方法高血压患者(高血压组)138例,健康人(对照组)141例。两组年龄、体质量指数无差异。对两组进行血压测量,空腹采血检测血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇等。聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行DNA多态性分析,琼脂糖凝胶电泳判断基因型。结果检测到TY、TC、CC 3种基因型。在高血压与对照组之间基因型构成比差异有统计学意义(P<0.05)。在高血压组TC-CC基因型和C等位基因频率(30.43%和17.75%)显著高于对照组(分别为19.86%和10.64%),P=0.042和0.016。TT基因型比TC-CC基因型的空腹血糖更高,差异有统计学意义(P<0.05)。结论脑利钠肽T-381C基因多态性可能对高血压有影响,TC-CC基因型和C等位基因发生高血压的风险较大。     

miR-143/145基因多态性与大动脉粥样硬化型卒中遗传易感性的关系

目的探讨miR-143/145的编码基因启动子区域rs4705342多态性与中国汉族人群大动脉粥样硬化型(LAA)卒中的关系。方法基于南京卒中注册系统,连续纳入了2013年8月至2016年12月于南京军区南京总医院神经内科就诊的1 066例LAA卒中患者,同期纳入1 152例健康体检未患有心脑血管疾病以及动脉粥样硬化的当地成年(年龄≥18岁)汉族居民作为对照组。通过SNPscan技术对rs4705342进行基因分型。采用多因素回归分析方法分析rs4705342多态性与LAA卒中风险的相关性,并根据各风险因素进行分层分析。结果在显性模型中,携带TC/CC基因型较携带TT基因型者发生LAA卒中的风险降低(校正OR=0.79,95%CI:0.65～0.96,校正P=0.018)。分层分析显示,年龄≥60岁(OR=0.71,95%CI:0.54～0.95)、无糖尿病史(OR=0.76,95%CI:0.61～0.95)及无吸烟史(OR=0.74,95%CI:0.58～0.95)人群中,携带TC/CC基因型较携带TT基因型发生LAA卒中的风险显著降低(均P0.05)。结论 miR-143/145编码基因启动子区域rs4705342 TC/CC基因型与中国汉族人群较低的LAA卒中的发病风险相关。     

葡萄糖转运体9基因 rs3733591（C>T）的单核苷酸多态性与我国汉族人群原发性痛风发病的相关性研究

目的探讨葡萄糖转运体9（SLC2A9）基因 rs3733591（C>T）的单核苷酸多态性（SNPs）与我国汉族人群痛风发病及血尿酸水平的相关性,并分析其多态性与痛风患者、健康体检者 PBMCs SLC2A9 mRNA 表达的相关性。方法①采用 TaqMan?探针法检测痛风组（297例原发性痛风性关节炎患者）和健康对照组（211名健康体检者） rs3733591（C>T）位点的基因型,χ2检验比较2组基因型及等位基因分布频率,计算比值比（OR）及95%可信区间（95%CI）。②采用实时荧光定量-PCR（RT-qPCR）法检测46例间歇期痛风患者及40名健康对照组 PBMCs SLC2A9 mRNA 的表达水平,非参数检验比较各组变量间的差异,并分析与 rs3733591（C>T）多态性的相关性。结果 rs3733591（C>T）位点的 TT 基因型在痛风组的分布频率显著低于健康对照组（37.7%与48.3%,P=0.017）,携带 TT 基因型的个体罹患痛风的相对风险OR 为0.647（95%CI：0.452~0.925）。而等位基因 T 在痛风组中的分布频率为60.9%,显著低于健康对照组的69.2%（χ2=7.324,P=0.007）,携带等位基因 T 的个体罹患痛风的相对风险 OR 为0.695（95%CI：0.533~0.905）;等位基因 C 在痛风组中的分布频率为39.1%,显著高于健康对照组的30.8%（χ2=1.440,P<0.05）。痛风组中携带 TC 基因型个体的外周血单个核细胞 SLC2A9 mRNA 的表达水平显著高于携带 TT 基因型者,而痛风组及健康对照组携带其他基因型的个体 SLC2A9 mRNA 的表达差异无统计学意义（P>0.05）。有痛风石（30例）痛风患者与无痛风石（190例）痛风患者的基因型及等位基因分布频率差异无统计学意义（P>0.05）。结论本研究提示 SLC2A9基因 rs3733591（C>T）位点的多态性可能与我国汉族人群原发性痛风的易感性相关,而与痛风患者痛风石形成无关;等位基因 C 可能为痛风发病的风险因子,而 TT 基因型及 T 等位基因可能对痛风发病具有保护作用;其多态性可能通过影响 SLC2A9基因的转录表达水平来参与痛风的发病。     

转化生长因子-β1基因多态性与 HBV 感染风险的相关性研究

目的：探讨转化生长因子-β1（ TGF-β1）基因多态性与中国人群HBV感染敏感性的关系。方法：本研究为以中国人群为研究对象的病例-对照研究,随机纳入50例HBV感染者（观察组）和50例与病例组性别、年龄相匹配的健康者（对照组）。采用聚合酶链反应-限制性片段长度多态性分析法检测TGF-β1基因T29 C多态性。结果：病例组和对照组基因型和等位基因分布均有明显差异（χ2＝12.795, df＝2, P＝0.002;χ2＝10.895, df ＝1, P＝0.002）。携带基因型TC和CC感染HBV的风险显著升高（ OR＝4.227,95％CI：1.604～11.139, P＝0.004; OR＝8.250,95％CI：2.042～33.334, P＝0.003）。携带等位基因C较等位基因T感染HBV的风险显著升高（ OR＝2.631,95％CI：1.472～4.702, P＝0.001）。结论： TGF-β1基因T29C多态性可能与HBV感染风险有关。     

白细胞介素8基因多态性与卵巢癌发生的关系

目的研究白细胞介素8(IL-8)+781基因多态性与卵巢癌发生风险之间的关系。方法筛选卵巢癌患者为疖例组和年龄匹配的健康人为对照组,应用聚合酶链反应-限制性片段长度多态性分析检测IL-8+781基因多态性结果携带基因型TT发生卵巢癌的风险显著高于携带基因型CC(OR=3.385,95%CI:1.361~8.418;P=0.009),携带等位基因T发生卵巢癌风险显著高于等位基因C(OR=1.704,95%CI:1.122~2.590;P=0.013)。结论 IL-8+781基因多态性可能影响卵巢癌的发生。     

急性心肌梗死患者C反应蛋白基因启动子T-757C多态性分析

目的探讨中国苏皖地区汉族人群C反应蛋白(CRP)基因启动子T-757C多态性与急性心肌梗死(AMI)的相关性。方法以303例AMI患者(AMI组)和282例非冠心病者(对照组)作为研究对象,应用聚合酶链反应-限制性片段长度多态性方法检测C反应蛋白基因T-757C多态性。结果 TC基因型频率在AMI组比对照组明显增高(41.3%vs31.2%,P=0.012),TT基因型频率、CC基因型频率和T等位基因频率在两组人群中(分别是55.8%vs63.5%、3.0%vs5.3%和76.4%vs79.1%)的分布无显著性差异(P值分别为0.058、0.210和0.272)。在调整吸烟、SBP、DBP、Glu、TG、LDL-C、HDL-C等危险因素并经多元Logistic回归分析显示CRP基因T-757C多态性TC基因型与AMI的发生仍呈显著性相关(OR=1.650,95%CI:1.031-2.640,P=0.037)。结论在中国苏皖地区汉族人群中,CRP基因启动子T-757C多态性与AMI的发病密切相关,TC基因型可能是AMI遗传易感性的基因标记之一。     

Haplotype analysis of the prostacyclin synthase gene and essential hypertension.

Previously, we discovered 3 polymorphisms in the prostacyclin synthase (PGIS) gene: 1) T-192G, in the 5-flanking region, a novel single-nucleotide polymorphism (SNP) that is not associated with essential hypertension (EH); 2) a variable number of tandem repeat (VNTR) polymorphism, 6 nucleotides upstream from the ATG start codon, that is associated with risk of cerebral infarction; and 3) C1117A, in exon 8, an SNP that does not cause an amino acid change in codon 373, and that is associated with risk of myocardial infarction (MI). The purpose of the present study was to establish haplotypes of the PGIS gene consisting of these 3 polymorphisms, and to assess the association between these haplotypes and EH. We detected 19 haplotypes. There was no significant difference in the overall distribution of haplotypes between EH and normotensive subjects. To summarize, we successfully identified haplotypes of the PGIS gene, and these haplotypes were not associated with EH.     

Association study between a novel single nucleotide polymorphism of the promoter region of the prostacyclin synthase gene and essential hypertension.

The purpose of this study was to investigate whether an association exists between the promoter region of the prostacyclin synthase gene and essential hypertension (EH). Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a novel single nucleotide polymorphism (SNP), T-192G, in the 5'-flanking region. We performed an association study using the SNP in 200 patients and 200 controls. The allele frequency distribution in the two groups was not significantly different. Thus, this SNP in the PGIS gene is not associated with EH.     

Synergistic effects of gene polymorphisms of the renin–angiotensin–aldosterone system on essential hypertension in Kazakhs in Xinjiang

Objective: To assess the synergistic effects of gene polymorphisms of the renin–angiotensin–aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs in Xinjiang. Methods: A cross-sectional case-control association study was conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity on eight common single nucleotide polymorphisms (SNPs) interspersed over five genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Interactions among the SNPs were analyzed by the multifactor dimensionality reduction method (MDR). Results: In single-locus analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR: 0.683; 2.025). Interaction analysis by MDR showed that there was a strong synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction between both ACE I/D and CY11B2 T-344C and AGT A-6G. Conclusions: There was a strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 -344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D were associated with male and female EH, respectively. H1 and H3 of AGT were protective and risk haplotypes, respectively.     

肾素-血管紧张素系统基因多态性与原发性高血压左心室肥厚关系的探讨

目的　探讨肾素 血管紧张素系统 (RAS)基因多态性与原发性高血压左心室肥厚 (EH LVH)的相关性以及在EH LVH产生中的多基因协同作用。方法　对 10 9例原发性高血压病 (EH)患者 ,采用聚合酶链反应 (PCR)以及聚合酶链反应 限制性片段长度多态性方法检测血液白细胞染色体DNA中血管紧张素转换酶 [ACE(I D) ]、血管紧张素原 [AGT(M2 35T) ]和血管紧张素Ⅱ 1型受体 [AT1 R(A116 6C) ]基因多态性 ;利用超声心动图检测左心室质量 (LVM)并计算左心室质量指数 (LVMI)。结果　ACE(I D)基因多态性D等位基因频率在EH LVH组中明显增高 (χ2 =4 .6 9,P=0 .0 30 ) ,男性EH患者中 ,ACE(I D)基因型构成比与LVH有关联 (χ2 =9.5 5 ,P =0 .0 0 8)。协同存在AGT TT型时 ,ACE(I D)基因多态性与EH LVH有关 (χ2 =6 .2 2 ,P =0 .0 4 4 ) ,且D等位基因在EH LVH明显增高 (χ2 =6 .91,P =0 .0 0 9) ,该类EH患者发生LVH的相对危险度增高 (OR :2 .5 0 ,95 %CI:1.2 5～ 5 .0 0 )。结论　ACE(I D)基因多态性D等位基因可能是LVH的独立危险因子。ACE基因多态性与AGT基因多态性之间的协同效应表明 ,同时携带AGT TT型时 ,具有ACE(I D)基因多态性D等位基因的EH患者更易发生LVH。     

A novel missense mutation of exon 3 in the type A human natriuretic peptide receptor gene: possible association with essential hypertension.

The natriuretic peptide (NP) family is involved in regulation of blood pressure and fluid volume. We recently characterized the exon/intron organization of the human type A NP receptor (hNPRA) gene. The aim of this study was to isolate the genetic markers according to the organization of this gene, and to study the association between this gene and essential hypertension. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we identified a novel missense mutation, M3411, consisting of a methionine (ATG) to isoleucine (ATC) substitution at nucleotide 1023 in exon 3. Computer-aided three-dimensional structural analysis suggested that M341 exists in the loop between two alpha-helices, and that the mutation may influence receptor activities by altering the conformation of the alpha-helices. We performed an association study of the mutation in 210 essential hypertension (EH) patients and 210 normotensive controls. The overall distribution of alleles was not significantly different between the control and EH groups. However, the C/C homozygous genotype was found only in the EH group. The ratio of plasma brain natriuretic peptide (BNP)/mean blood pressure of the C/C genotype was significantly higher than that of the G/G genotype or the G/C genotype. We conclude that the significance of homozygous M3411 mutation in exon 3 is worth investigating for its possible association with EH.     

醛固酮合酶基因多态性与原发性高血压及血浆醛固酮水平的关系

目的　探索武汉地区汉族人群中醛固酮合酶 (CYP11B2 )基因 3 44C/T多态性与原发性高血压 (EH)的相关性 ,及高血压人群醛固酮合酶CYP11B2基因 3 44C/T多态性与血浆醛固酮(pAldo)水平的相关性。方法　应用PCR RELP技术对 2 0 4例CYP11B2基因 3 44C/T多态性进行分析 ,应用放射免疫法测定 10 6例EH组的血浆醛固酮水平。结果　CYP11B2基因 3 44C/T多态性以TT和CT为主要基因型 ,与EH无明显相关性 (P >0 .0 5 )。高血压患者血浆醛固酮水平在CYP11B2基因 3 44C/T的 3个不同基因型组比较差异有显著性 (P <0 .0 1)。结论　武汉地区汉族人群CYP11B2基因 3 44C/T多态性频率与EH没有明显相关性。高血压人群的血浆醛固酮水平与CYP11B2基因 3 44C/T多态性相关     

基质金属蛋白酶-9基因C1562T多态性与高血压颈动脉粥样硬化关系

目的:研究基质金属蛋白酶-9(MMP-9)基因C1562T多态性与高血压颈动脉粥样硬化的相关性。方法:原发性高血压患者120例,测定受试者双侧颈动脉内-中膜厚度(IMT),IMT≥1.3mm认为存在粥样硬化斑块。依颈动脉有无粥样硬化分为颈动脉粥样硬化组、颈动脉正常组。用聚合酶链反应-限制性片段长度多态性分析法分析2组患者的MMP-9基因C1562T的多态性。结果:颈动脉粥样硬化组与颈动脉正常组CT TT基因型频率分别为28.8%、13.2%,差异有统计学意义(χ2=4.488,P=0.034),T等位基因与颈动脉粥样硬化发病密切相关(OR=2.092,95%CI:0.991~4.419,P=0.047)。结论:MMP-9T等位基因与高血压颈动脉粥样硬化密切相关,可能是其遗传标志。     

Haplotype analysis of PPARγ C681G and intron CT variants

Background

There is strong evidence suggesting an association between the peroxisome-activated receptor γ (PPARγ) gene and multimetabolic disorders. The association of PPARγ genetic variants with essential hypertension (EH) has not yet been investigated. The aim of this study was to investigate the association between the PPARγ gene (C681G and intron CT) and EH, examining the polymorphism and haplotype in a Han Chinese population.

Methods

Participants were recruited within the framework of the PMMJS cohort population survey in an urban community of Jiangsu Province, China. Two single-nucleotide polymorphisms (SNPs) previously reported to be associated with multimetabolic disorders and the reasonable coverage of the PPARγ gene region were analyzed with TaqMan SNP genotyping assays.

Results

C681G and intron CT were significantly associated with an increased risk of EH both in the codominant model and the dominant model after adjusting for potential nongenetic risk factors. Analysis of the haplotype association revealed that the risk of EH was significantly increased among individuals carrying the GC (odds ratio, 95?% CI: 1.60, 1.21–2.11), CT (1.45, 1.03–2.11), and GT haplotypes (1.95, 1.17–3.23) compared with those carrying the CC haplotype.

Conclusion

The polymorphisms of C681G and intron CT were significantly associated with the risk of EH, and the GC, CT, and GT haplotypes established by C681G and intron CT are likely to be genetic markers of EH in the Han Chinese population.     

内皮脂肪酶584C/T基因多态性与高血压病相关性研究——299例常州地区汉族人群分析

目的探讨内皮脂肪酶（EL）584C／T基因多态性与高血压病（EH）的相关性。方法本研究共纳入160名EH患者和139名对照者。EL584C／T基因型检测采用聚合酶链反应一限制性内切酶片段多态性（PCR．RFLP）方法检测。结果EH组CC、CT、TT基因型频率分别为56．3％,42．5％,1．1％;对照组CC、CT、TT基因型频率分别为56．1％,38．8％,5．0％。T等位基因频率在两组间分别为22．5％和24．5％。两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。Logistic回归显示在矫正传统的EH高危因素后,EL584C／T多态性仍然与EH之间无相关性。本研究同时表明EL584C／T多态性与血脂之间无明显相关性。结论EL584C／T基因多态性与常州地区汉族人群EH之间无明显相关性。