内皮素受体A基因多态性与中青年原发性高血压的相关性研究

目的:探讨陕西地区汉族中青年人群中内皮素受体A(EDNRA)单核苷酸基因多态性(SNP)与原发性高血压易感性的关系。方法:选择2015年1月至2018年1月,在本院治疗的338例中青年(18～45岁)原发性高血压(EH)患者作为EH组,另外选择300例中青年健康志愿者作为对照组。采用聚合酶链反应联合DNA直接测序法检测EDNRA基因rs1801708和rs5335位点多态性。结果:EH组和对照组比较,两组rs5335位点等位基因分布频率,差异具有统计学意义(P<0.05),rs1801708位点基因型和等位基因分布频率,差异均无统计学意义(均P>0.05)。按BMI值分层,在BMI<25 kg/m~2中青年人群中,EH组rs5335位点基因型/等位基因分布频率在共显性基因模型、隐性基因模型和等位基因模型下与对照组比较,差异均具有统计学意义(均P<0.05),两组rs1801708位点基因型/等位基因分布频率在各种基因模型下,差异均无统计学意义(均P>0.05);在BMI≥25 kg/m~2中青年人群中,两组比较rs5335和rs1801708位点基因型/等位基因分布频率在各种基因模型下,差异均无统计学意义(均P>0.05)。多因素分析结果显示,携带EDNRA基因rs5335位点C等位基因可降低BMI<25 kg/m~2中青年人群EH的发生风险(OR=0.484, 95%CI:0.361～0.836,P=0.007)。结论:EDNRA基因rs5335位点多态性与陕西地区汉族中青年人群EH发生相关。     

贵州汉族、苗族和布依族原发性高血压与载脂蛋白E基因单核苷酸多态性的关系

目的 探讨载脂蛋白E(ApoE)基因单核苷酸多态性(SNP)与贵州汉族、苗族、布依族人群原发性高血压(EH)的关联性。方法 通过病例-对照研究方法,选取贵州雷山苗族、荔波布依族及贵阳汉族原发性高血压患者343例(苗族110例,布依族119例,汉族114例)和健康对照335例(苗族111例,布依族117例,汉族107例),并收集年龄、性别、身高、体质量、空腹血糖、总胆固醇、三酰甘油等临床资料和生化指标,采用t检验或χ²检验比较两组临床资料与生化指标的差异。分别采用Sequenom MassARRAY和竞争性等位基因特异性PCR(KASP)基因分型技术对以上人群ApoE基因5个SNP位点(rs7259620、rs440446、rs769449、rs1065853、rs439401)和2个SNP位点(rs429358、rs7412)进行基因分型,采用logistic回归分析ApoE基因多态性与贵州人群EH的遗传关系。结果 在贵州苗族和布依族人群中,没有发现与EH关联的SNP位点。汉族人群rs439401等位基因及基因型在EH组和对照组的分布差异具有统计学意义(χ     

内皮型一氧化氮合成酶基因rs3918181多态性与贵州省苗族、布依族原发性高血压的关系

目的:探讨贵州省苗族、布依族人群内皮型一氧化氮合成酶(eNOS)基因第14内含子rs3918181位点多态性与原发性高血压的关系。方法:选取贵州雷山县苗族和荔波县布依族247例原发性高血压患者(苗族123例,布依族124例)为高血压组,244例健康人群(苗族118例,布依族126例)为对照组。采用TaqMan探针法检测eNOS基因rs3918181位点多态性,分析rs3918181位点不同基因型及等位基因频率在两个民族人群中的分布。结果:eNOS基因rs3918181位点AA、AG、GG基因型及A、G等位基因在苗族、布依族高血压组与对照组中的分布频率符合Hardy-Weinberg平衡定律;贵州苗族、布依族人群eNOS基因rs3918181位点基因型分布频率及等位基因频率在高血压组和健康对照组之间差异无统计学意义。结论:eNOS基因rs3918181位点多态性与贵州省苗族、布依族人群原发性高血压可能不相关,该位点多态性在贵州苗族、布依族人群之间无民族差异性。     

血管紧张素Ⅱ1型受体基因rs388915多态性与原发性高血压的相关性

目的:研究血管紧张素Ⅱ1型受体(angiotensinⅡtype 1 receptor,AT1R)基因rs388915多态性与汉族人群原发性高血压(EH)的相关性,为EH的诊断、治疗及易感性研究提供依据。方法:选取在北京安贞医院就诊的北方汉族原发性高血压患者640例(EH组)和442例体检血压正常者(正常对照组NT),应用荧光定量聚合酶链反应方法进行AT1R基因rs388915位点的多态性检测,比较不同分组人群的差异。结果:rs388915位点在EH组和NT组的基因型分别为GG型23/8、AG型211/125、AA型393/305;G等位基因频率分别为79.5%/83.9%,A等位基因频率分别为20.5%/16.1%。2组之间基因型和等位基因频率差异有统计学意义(分别为P=0.03;P=0.01)。显性模型、加性模型在2组间差异有统计学意义(P=0.019;P=0.03)。根据性别进行亚组分析,在女性人群中,EH组和NT组基因型分别为GG型7/3、AG型87/51、AA型132/127,2组之间基因型频率有差异(P=0.045);G等位基因频率28.7%/15.7%和A等位基因频率71.3%/84.3%,发现2组差异无统计学意义(P=0.000)。男性人群中,2组(EH/NT)患者基因型分别为GG型6/5、AG型124/74、AA型261/178,2组间差异无统计学意义(P=0.26);G等位基因频率19.5%/16.3%和A等位基因频率81.5%/83.7%,2组间差异无统计学意义(P=0.15)。经Logistic逐步回归分析,rs388915等位基因与EH发病密切相关(P=0.024,OR=1.341,95%Cl=1.039～1.1731)。结论:AT1R基因rs388915多态性可能与中国北方汉族人群原发性高血压的发病有关,特别是在女性人群中。     

上皮细胞钠离子通道β亚单位基因SCNN1B多态性与原发性高血压的关系研究

目的研究上皮细胞钠离子通道β亚单位基因SCNN1B羧基端单核苷酸多态性与北京市汉族高血压家系原发性高血压的关系。方法在北京市汉族常住人群中纳入原发性高血压家系108个(433人),分成高血压患者组(229人)、高血压患者第一代和第二代亲属(血压正常)组(118人)和高血压患者配偶(血压正常)组(86人)。检测生化指标及心电图Sv1+Rv5数值,并分析SCNN1B基因13号外显子及两翼部分单核苷酸多态性。结果在SCNN1B基因13号外显子的两翼部分符合最小等位基因频率≥5%的位点只有两个即rs3743966(A/T)、rs34618783(A/G)。3组间比较,高血压组的AA/rs3743966基因型频率明显高于其他两组(55.5%比44.9%和32.6%,χ2=13.768,P<0.01),TT基因型频率明显低于其他两组(9.6%比15.3%和38.3%,χ2=37.205,P<0.01)。rs34618783位点基因型频率在3组间比较,差异无统计学意义。TT/rs3743966纯合子组的收缩压和舒张压水平比AA纯合子组平均低15.69 mmHg和9.14 mmHg,差异有统计学意义(均为P<0.01),其他生化指标在3组间比较差异均无统计学意义(均为P>0.05)。多因素Logistic回归分析显示,TT/rs3743966基因型进入方程(OR:0.239,95%CI:0.117⁰.489,P<0.001)。结论 SCNN1B基因rs3743966位点TT基因型可能是北京市汉族高血压家系原发性高血压的保护性因素之一。     

原发性高血压SCNN1G基因多态性特征分析

目的:本实验通过分析SCNN1G基因rs5729的基因型及等位基因分布特点,探究此基因单核苷酸多态性与原发性高血压(EH)的关系。方法:采用高分辨率熔解曲线法(high resolution melting,HRM)对rs5729位点进行基因多态性分型检测。样本来自2018-06-2019-07吉林市中心医院高血压患者115例(病例组)和非高血压人群88例(对照组)。同时,在上述样本中随机选取81例采用测序法进行验证。结果:病例组的基因型频率是TT 67.82%、AT 25.22%、AA 6.96%,T、A等位基因频率分别为80.43%和19.57%;对照组中rs5729位点TT、AT、AA基因型频率分别为89.77%、9.10%、1.13%;T、A等位基因频率分别为94.32%和5.68%;病例组和对照组的基因型与等位基因频率在2组间分布差异有统计学意义(P0.05)。结论:利用HRM法对SCNN1G rs5729位点进行基因分型,发现其在高血压人群中分布存在差异。     

乙醛脱氢酶2基因 rs671多态性和新疆汉族人群原发性高血压的关联性研究

目的：探讨乙醛脱氢酶2（ALDH2）基因 rs671多态性在新疆地区汉族人群原发性高血压（EH）发病中的作用。方法应用 Taqman 技术检测了474例汉族 EH 患者和358例正常血压者 ALDH2基因 rs671多态性。结果在男性人群中,饮酒组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于不饮酒组（P ＜0．01）;EH 组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于对照组（P ＜0．01）。而在女性人群中,EH 组和对照组 rs671的 3 种基因型频率和等位基因频率的分布差异无统计学意义（P ＞0．05）。非条件 Logistic 回归分析校正年龄、体重指数、糖尿病史、饮酒史等影响因素后,在男性人群中 rs671的 GA ＋AA 基因型者患 EH 的风险低于 GG基因型者（OR ＝0．656,95％CI：0．448～0．962,P ＜0．05）,GA ＋AA 基因型者收缩压水平明显低于GG 型者（P ＜0．05）。而在男性不饮酒者和女性人群中,GA ＋AA 基因型者和 GG 基因型者血压水平比较差异无统计学意义。结论ALDH2基因 rs671多态性可能和新疆汉族男性人群 EH 的发生相关,rs671的 GA ＋AA 基因型可能是汉族男性人群 EH 的一个保护因素。     

白介素27基因多态性与克罗恩病的相关研究

目的:探讨白介素27(IL-27)基因rs153109、rs17855750和rs181206位点的多态性与克罗恩病的相关性。方法:选取145例汉族克罗恩病患者和238名正常人作为观察对象,采用聚合酶链反应-连接酶检测进行基因分型,分析病例组和对照组的基因型频率及等位基因频率。结果:2组的基因型分布均符合Hardy-Weinberg平衡定律(P>0.05)。rs153109位点的C等位基因频率在2组之间的分布差异有统计学意义(45.86%比38.24%,P0.05);rs17855750和rs181206位点的基因型频率及等位基因频率在2组间的分布差异无统计学意义(P>0.05)。结论:IL-27基因多态性位点rs153109可能与克罗恩病易感性有关,未发现rs17855750和rs181206多态性与克罗恩病有关。     

内皮型一氧化氮合酶基因G894T多态性与宁夏回、汉族原发性高血压的关系

目的:研究宁夏地区回、汉族原发性高血压(EH)人群与内皮型一氧化氮合酶(eNOS)基因G894T多态性之间的关系。方法:收集宁夏回族142例EH患者(回EH组)、112例正常血压者(回对照组)及宁夏汉族158例EH患者(汉EH组)、176例正常血压者(汉对照组),应用PCR-RFLP技术进行eNOS G894T基因多态性的检测,统计分析该位点不同基因型及等位基因频率在两族人群中的分布。结果:回EH组与回对照组,汉EH组与汉对照组,回、汉EH组间与回、汉对照组间基因型及等位基因频率差异无统计学意义。结论:eNOS基因G894T多态性与宁夏地区回、汉族人群EH发病无关;该位点多态性在宁夏回、汉族人群之间无种族差异性。     

CTRP9基因多态性与冠心病的相关性

目的探讨广东地区汉族人群CTRP9基因多态性与冠心病遗传易感的相关性。方法入选冠心病患者548例和对照个体862例,利用聚合酶链式反应-连接酶检测反应(PCR-LDR)技术检测CTRP9基因的两个多态性位点rs6583、rs9553238的基因型,并采用Logistic回归分析两个多态位点和冠心病的易感性。结果 rs6583和rs9553238的等位基因、基因型频率在广东地区汉族人群的冠心病组和对照组分布中均无统计学差异(P>0.05),构建的显性模型、隐性模型、加性模型在冠心病组和对照组中也无统计学差异(P>0.05);CTRP9基因单体型(rs6583-rs9553238)在这两组中仍未发现有统计学差异(P>0.05)。结论 CTRP9基因rs6583和rs9553238多态位点与广东地区汉族人群的冠心病遗传易感无显著相关性。     

A common missense single nucleotide polymorphism in the E-selectin gene is significantly associated with essential hypertension in the Han population but only weakly associated in the Uygur population

Experimental and clinical observations suggest that E-selectin could have an important role in essential hypertension (EH), but the relationship between common E-selectin variants and EH has not been extensively studied in the Chinese population. In this study, we explored the association between two common variants in the E-selectin gene (rs5361A/C and rs5355C/T) and EH in the Uygur, Kazakh and Han populations in the Xinjiang area. A case-control study was conducted to explore the association between these two single-nucleotide polymorphisms and EH in a large sample size, including 941 EH subjects (309 Uygur, 264 Kazakh and 368 Han individuals) and 924 control subjects (300 Uygur, 275 Kazakh and 349 Han individuals). Univariate analysis showed that the rs5361 A/C polymorphism was significantly associated with EH in the Uygur (P=0.002) and Han (P=3.6 × 10(-7)) populations. The CC genotype of this SNP was present only in patients with EH in all of the three nationalities studied. Han individuals who carry the CC genotype of rs5361 were more susceptible to EH, according to the dominant models (P=1.13 × 10(-4), odds ratio=3.812, 95% confidence interval: 1.685-7.792), but there was no association of genotype with EH for the other ethnicities. No significant difference in rs5355 C/T polymorphism rate was found between the EH and control groups. Our results indicate that the common variant rs5361 is strongly associated with EH in Han individuals and weakly associated in Uygur individuals. The CC genotype of rs5361 might be an independent risk factor for EH among Uygur, Kazakh and Han individuals in the Xinjiang area.     

转化生长因子β_1基因标签单核苷酸多态性与新疆汉族原发性高血压相关性研究

目的 研究转化生长因子β_1(TGF-β_1)基因标签单核苷酸多态(tSNP)及血浆水平与新疆汉族原发性高血压(EH)的关系,阐明连锁不平衡(LD)模式以及单体型分布特征.方法 采用整群抽取随机抽样的方式,以新疆沙湾县732例汉族人(EH组365例,对照组367例)为研究对象,进行流行病学调查和临床检查,并采集血样.用双抗体夹心法(ELISA试剂盒)测量TGF-β_1血浆浓度.SNaPshot方法进行基因分型.结果 (1)TGF-β_1基因rs11466345位点等位基因A、G在EH组和对照组中分布频率分别为69.7%、30.3%、74.4%、25.6%,EH组G等位基因频率高于对照组(x2=3.949,P=0.047),G等位基因患病风险为A等位基因1.261倍(95%CI 1.003～1.585,P=0.047),其他tSNP基因型及等位基因频率在EH组和对照组分布差异元统计学意义(P>0.05).(2)除m11466345位点外,其他tSNP位点间存在强LD,其构成的单体型频率在EH及对照组中分布差异无统计学意义(P>0.05).(3)TGF-β_1基因tSNP在EH组与对照组各基因型和等位基因之间TGF-β_1血浆水平差异无统计学意义(P>0.05).结论 TGF-β_1基因rs 11466345G等位基因可能是新疆汉族EH的遗传易感基因,其他tSNP可能与该民族EH不相关,除rs11466345位点外,其余tSNP位点间存在强LD,其构成的单体型与EH无关;在新疆汉族人群中TGF-β_1基因tSNP与TGF-β_1血浆水平不相关.     

CACNA1C rs1006737 SNP increases the risk of essential hypertension in both Chinese Han and ethnic Russian people of Northeast Asia

Voltage-gated Ca²⁺ channels play a key role in the regulation of arterial tone and blood pressure. The aim of this study was to determine whether the association of calcium voltage-gated channel subunit alpha1 C (CACNA1C) rs1006737 with essential hypertension (EH) exists in both Chinese Han and ethnic Russian populations of Northeast Asia. We used a case-control study of 2 ethnic groups in the same latitude geographical area to investigate the association between the susceptibility of EH and rs1006737 polymorphism. A total of 1512 EH patients and 1690 controls in Chinese Han people (Heilongjiang Provence, China), 250 EH patients, and 250 controls in ethnic Russian people (Chita, Russia), participated in this study. All participants were genotyped using the TaqMan SNP genotyping assay (Agena Company). Baseline characteristics and the minor allele frequencies of rs1006737 vary substantially among common Chinese Han and ethnic Russian people. Allele A was found to be a risk factor for EH in Chinese Han [(odds ratio) OR 1.705, (confidence interval) 95% CI: 1.332–2.182, P < .001] and ethnic Russian (OR 1.437; 95% CI: 1.110–1.860, P = .006). The GA genotype was significantly associated with an increased risk of hypertension (OR 1.538, 95% CI: 1.188–1.991, P = .001) for Chinese Han people, and the AA genotype (OR 2.412, 95% CI: 1.348–4.318, P = .003) for ethnic Russian people. The results of this study indicate that the A allele of the variant rs1006737 in the CACNA1C gene may be a useful genetic marker for EH risk prediction in Chinese Han and ethnic Russian populations.     

The ALDH2 gene rs671 polymorphism is not associated with essential hypertension

Essential hypertension (EH) is a worldwide problem. Acetaldehyde dehydrogenase 2 (ALDH2) gene has been suggested to be correlated with EH. However, the results are inconsistent. This study aimed to investigate the associations of ALDH2 rs671 polymorphism with EH in a Chinese Han population in Shanghai. Genotype of ALDH2 rs671 was analyzed in 1923 EH patients and 1115 control subjects. We found no association between ALDH2 rs671 and EH risk or EH-related quantitative blood chemistry values. Furthermore, a meta-analysis was performed and the summary results from 11220 patients and 8339 control subjects were consistent with our findings. These results indicated that rs671 of ALDH2 may not associate with the risk of EH.     

Association of the human CYP11B2 gene and essential hypertension in southwest Han Chinese population: a haplotype-based case-control study

Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure (BP). The aldosterone-synthase gene (CYP11B2) has been regarded as a candidate gene for essential hypertension. To address this issue, we carried out a haplotype-based, case-control study to explore the association between a human CYP11B2 gene and essential hypertension (EH) in the southwest Han population of China (n = 1020 individuals). Four tag single-nucleotide polymorphisms (SNPs) (rs4536, rs4545, rs3097, and rs3802230) and the C-344T polymorphism, as well as the K173R polymorphism in the CYP11B2 gene, were genotyped using the PCR-RFLP method. Single-locus analysis showed that the C allele of rs3802230 was significantly more prevalent in the EH subjects as compared to control subjects, adjusted for covariates. Haplotype analysis showed that the haplotype AAGC constructed by the tag SNPs (rs4536, rs4545, rs3097, and rs3802230), which carried the susceptible rs3802230 C allele, significantly increased the risk of essential hypertension with an odds ratios equal to 3.56 (P = 0.0001). The present results indicated that the rs3802230 C allele might be a risk marker for essential hypertension and haplotype AAGC might confer high genetic susceptibility to essential hypertension in a southwest Han Chinese population.     

广东汉族原发性高血压患者CYP2C9和ACE基因多态性的分布特征

目的:观察沙坦类药物代谢酶细胞色素氧化酶P450 2C9(CYP2C9)基因的多态性和血管紧张素Ⅰ转换酶(angiotension I-coverting enzyme,ACE)基因的多态性在广东汉族原发性高血压(essential hypertension,EH)患者中的分布特征。方法:应用PCR、基因测序及琼脂糖凝胶电泳等方法,对206例EH患者CYP2C9和ACE基因型进行检测分析。结果:广东汉族EH患者中CYP2C9基因的1075位C等位基因的频率为3.2%,广东汉族EH患者中CYP2C9*3等位基因的频率与广东人群相比,无显著性差异;ACE基因D、I等位基因的频率分别为56.3%和43.7%。ACE基因的D等位基因频率显著高于广东及国内其他地区正常人群中的频率(P0.05)。结论:在广东汉族EH患者中,未发现CYP2C9*3等位基因与EH有关,而ACE基因的D等位基因可能和EH有关,同时,对EH患者进行CYP2C9和ACE基因的基因型的检测,可能对临床个体化降压治疗具有一定的指导意义。     

Association of CLCNKB Haplotypes and Hypertension in Mongolian and Han Populations

We investigated a possible association between genetic variations in chloride channel Kb (CLCNKB) gene and essential hypertension (EH) in the Mongolian and Han populations in Inner Mongolia. Our study included 414 unrelated Mongolian herdsmen and 524 Han farmers. Two tagSNPs of CLCNKB (rs945393 and rs10803414) were identified from the Chinese HapMap database based on pairwise r² ≥ 0.5 and minor allele frequency ≥0.05. Genotyping was performed using the PCR/ligase detection reaction assay. There was significant difference in allele frequency of rs10803414 between the EH group (35%) and the control group (26%) in the Mongolian population (P < .05). Significant association was identified between rs10803414 and EH in the Mongolian population (P < .05) and rs945393 and EH in the Han population (P < .01). The frequency of haplotype CC in the EH group (9.4%) was significantly higher than in the control group (4.6%) in the Mongolian population; individuals who possessed the CC haplotype had a significantly higher risk of EH in the Mongolian population. There was no association between haplotype and EH in the Han population. After adjusting for age, sex, and other confounding risk factors, only rs10803414 was the risk factor of hypertension in Mongolians. Our results indicate that rs10803414 in CLCNKB confers a significant risk of EH in the Mongolian population and haplotype CC of CLCNKB is a genetic factor for EH in the Mongolian population. Our study expands the association between CLCNKB and EH to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of EH locus.     

The obesity-related polymorphism PCSK1 rs6235 is associated with essential hypertension in the Han Chinese population

Proprotein convertase subtilisin/kexin-type 1 (PCSK1) is a prohormone convertase that has an important role in prohormone maturation including the process of prorenin to renin. We studied the association of the PCSK1 single-nucleotide polymorphism (SNP) rs6235 (encoding an S690T substitution) with essential hypertension (EH), obesity and related traits in the Han Chinese population. The rs6235 SNP in the PCSK1 gene was investigated using a case-control study design, with 1034 hypertension cases and 1112 normotensive controls. In this study, the rs6235 SNP was significantly associated with hypertension (OR=1.26, 95% CI (1.10-1.46), P=0.001); the odds ratios of GC vs GG and CC vs GG were 1.30 (95% CI (1.06-1.58), P=0.010) and 1.55 (95% CI (1.12-2.13), P=0.007), respectively. In the controls, the C-allele was associated with increased systolic (P=0.010) and diastolic (P=0.010) blood pressure levels. In all of the EH patients and EH patients without a history of renin-angiotensin-aldosterone (RAA) system-related antagonists, the C-allele was associated with increased plasma renin activity (P=0.00004 and 0.002, respectively) and aldosterone levels (P=0.018 and 0.005, respectively). The C-allele was also associated with increased body mass index (BMI) (P=0.010) in the normotensive controls. In conclusion, the PCSK1 SNP rs6235 was associated with EH and blood pressure in the Han Chinese population, and this association may be mediated by the SNP's effect on RAA levels. rs6235 was also associated with BMI in this population.