新疆哈萨克族内皮型一氧化氮合酶基因rs7830和rs3918188多态性与原发性高血压的相关性

目的:探讨新疆哈萨克族内皮型一氧化氮合酶(eNOS)基因rs7830和rs3918188位点多态性与原发性高血压(EH)的相关性。方法:采用流行病学的病例-对照研究方法,用经典的酚-氯仿法进行DNA抽取、PCR及纯化,用SNaPshot分型技术对新疆哈萨克族363名EH患者(EH组)和370名正常血压者(NT组)进行eNOS基因rs7830和rs3918188分型,并采用生化技术测定空腹血糖、尿酸、胆固醇、甘油三酯等10项血浆指标,测定体重指数、腰臀比等指标。结果:(1)年龄(P<0.01)、体重指数(P<0.01)、甘油三酯(P<0.01)、低密度脂蛋白(P<0.05)和载脂蛋白A1/B(P<0.05)是新疆哈萨克族EH发生的影响因素;(2)新疆哈萨克族eNOS基因rs7830和rs3918188位点的基因型和等位基因频率在2组分布均无差异(P>0.05);(3)新疆哈萨克族eNOS基因rs7830和rs3918188位点所构建的CA、CC、AC和AA 4种单倍型频率在2组中分布均无差异(P>0.05)。结论:(1)年龄、体重指数和甘油三酯是新疆哈萨克族EH发生的危险因素,而低密度脂蛋白和载脂蛋白A1/B是新疆哈萨克族EH发生的保护因素;(2)新疆哈萨克族eNOS基因rs3918188和rs7830位点多态性与EH的发生均不相关。     

血管内皮细胞功能相关基因多态性与子痫前期的遗传易感性研究

目的探讨血管内皮细胞功能相关基因即内皮型一氧化氮合成酶(eNOS/NOS3)、血管内皮生长因子(VEGF)、胰岛素样生长因子(IGF1)基因的单核苷酸多态性(SNP)与子痫前期(PE)发病的相关性。方法选取2014年7月至2015年5月于南方医科大学附属深圳妇幼保健院分娩的汉族妇女442例,采用SNapshot技术对eNOS、VEGF、IGF基因5个位点进行检测,分析两组间基因型及等位基因频率的差异。结果 (1)深圳地区汉族妇女中暂未发现存在IGF1基因rs5742620位点、NOS3基因27bp-VNTR in intron 4位点的多态性。(2)PE组NOS3基因rs2070744位点AA基因型、A等位基因频率明显低于对照组(95.5%vs99.3%,P=0.007,OR=0.14,95%CI为0.03-0.73;97.4%vs99.7%,P=0.003,OR=0.13,95%CI为0.028-0.632)。(3)PE与对照组比较,NOS3基因rs1799983位点GG、GT、TT基因型及等位基因分布无显著差异;VEGF基因rs3025039位点GG、AG、AA基因型及等位基因分布无显著差异。结论 (1)NOS3基因rs2070744位点可能与深圳地区汉族妇女PE发生有关。(2)NOS3基因rs2070744位点AA基因型、A等位基因可能是本群体PE发病的保护因素。(3)IGF1基因rs5742620位点、NOS3基因27bp-VNTR in intron 4位点为本群体的罕见突变。     

内皮固有型一氧化氮合酶基因单核苷酸多态性与冠心病的相关性研究

探讨内皮固有型一氧化氮合酶(ecNOS)基因的单核苷酸多态性(SNP)与冠心病(CAD)的相关性.提取107例CAD患者和132名健康对照者外周血有核细胞DNA,应用荧光标记单碱基延伸分型技术及寡核苷酸微阵列芯片杂交技术检测ecNOS基因的2个标签SNP(tag SNP)rs7830和rs3918188.结果发现CAD组rs7830的CC基因型频率和C等位基因频率明显低于健康对照组(P＜0.05).两组rs3918188的基因型频率及等位基因频率无统计学差异(P＞0.05).通过对2个SNP进行单倍型分析发现,CAD组和健康对照组的单倍型频率具有统计学差异(P<0.05).结果提示ecNOS基因 rs7830多态性变异及由rs7830和rs3918188构建的CA、AA单倍型是CAD的遗传危险因素.     

云南汉族ATP2B1基因标签SNPs与原发性高血压的关系

目的探讨Ⅰ型细胞膜钙离子转运酶(ATP2B1)基因标签单核苷酸多态(SNPs)与云南汉族原发性高血压(EH)的相关性。方法用聚合酶链式反应-限制性片段长度多态性方法,检测1020例云南汉族人(EH组和对照组各510例)ATP2B1基因12个标签SNPs(rs10506974、rs10506975、rs2854371、rs957525、rs3741895、rs2681472、rs2070759、rs12423192、rs1050395、rs11105357、rs11105358和rs7975689)和ATP2B1基因附近区域的rs17249754位点的多态性。结果 rs17249754位点基因型和等位基因频率在EH组和对照组间的分布均具有显著性差异(P0.01),Logistic回归分析发现,rs17249754位点AA基因型和A等位基因使EH患病风险显著性降低(OR=0.60,95%CI 0.40~0.89,校正P0.05;OR=0.73,95%CI 0.60~0.88,校正P0.01)。结论 ATP2B1基因附近区域rs17249754位点与云南汉族人群EH相关,rs17249754 A等位基因可能是降低云南汉族EH风险的保护因子。     

孕酮受体基因多态性在宁夏回、汉族人群中的分布特征

目的:探讨孕酮受体基因(PGR基因)rs590688、rs1042838、rs11224592三个单核苷酸多态性(SNP)位点在宁夏回、汉族人群的分布特征并与1000Genomes网站上公布的其他群体分布频率进行比较分析。方法:采用TaqMan探针基因分型方法分析宁夏回、汉族人群867例(回族335例,汉族532例)PGR 3个SNPs位点rs590688、rs1042838、rs11224592基因型及等位基因频率的分布情况。结果:宁夏回、汉族人群PGR基因rs590688和rs1042838两个位点基因型及等位基因频率分布差异无统计学意义;rs11224592位点基因型及等位基因频率在宁夏回、汉族人群的分布差异有统计学意义;3个SNP位点的基因型及等位基因分布频率在男、女性别间差异无统计学意义。宁夏人群PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因分布频率与1000Genomes网站公布的其他群体相比较,rs590688位点与欧洲人群及非洲人群差异均有统计学意义;rs1042838位点与欧洲人群的差异有统计学意义;rs11224592位点与非洲人群的差异有统计学意义。结论:PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因频率在宁夏回、汉族人群的分布中,rs590688和rs1042838两个位点的分布无民族差异;rs11224592位点的分布具有民族差异;3个SNP位点的分布无性别差异。PGR 3个SNP位点基因型及等位基因频率在不同种族和地区的分布不同。     

TLR7基因单核苷酸多态性与江苏淮安哮喘患者易感性的相关性研究

目的:探讨Toll样受体7(TLR7)基因rs179009、rs179019、rs5935436位点多态性与江苏淮安地区汉族人群支气管哮喘的相关性。方法:采用病例对照方法,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法比较158例支气管哮喘组与137例健康对照组之间基因型、等位基因频率的差异。结果:哮喘组TLR7基因rs179009、rs170019位点基因型及等位基因型频率与对照组相比差异有统计学意义(P<0.05)。rs5935436位点基因型及等位基因型频率在哮喘组和对照组间差异均无统计学意义(P>0.05)。结论:TLR7基因rs179009位点和rs179019位点的多态性可能与江苏淮安地区汉族人群哮喘相关;而rs5935436位点的多态性可能与江苏淮安地区汉族人群哮喘无关。     

新疆哈萨克族转化生长因子β1基因多态性及其血浆水平与原发性高血压的关系

目的 研究新疆哈萨克族原发性高血压(essential hypertension,EH)患者转化生长因子β1(transforming growth factor-β1,TGF-β1)+869T/C、+915G/C基因多态性及血浆水平与EH的关系.方法 采用聚合酶链反应-限制性片段长度多态性和基因测序对新疆哈萨克族365名EH患者及435名正常对照组进行基因分型,用双抗体夹心法测量TGF-β1血浆浓度.结果 +915G/C位点基因型GG、GC及等位基因G、C频率依次为97.9%、2.1%、98.77%、1.23%,EH组与对照组差异无统计学意义(P＞0.05);+869T/C位点基因型TT、TC、CC及等位基因T、C在对照组中频率依次为25.97%、46.67%、27.36%、49.3%、50.7%,CC基因型及C等位基因频率在EH组中高于对照组(41.60%vs.27.36%、62.2%vs.50.7%),差异有统计学意义(P＜0.05),C等位基因携带者EH患病风险高于T等位基因携带者(OR=1.6O,P=0.00).+869T/C与+915G/C存在连锁不平衡,其形成的单倍型C-G在EH组中频率高于对照组(61.6%vs.49.8%,P＜0.05).+869T/C及+915G/C基因型、等位基因在EH组和对照组中TGF-β1血浆水平差异无统计学意义(P＞0.05).结论 新疆哈萨克族TGFβ1+915G/C基因变异频率很低,且不存在纯合变异,+869位点C等位基因可能是哈萨克族EH的遗传易感基因,+869T/C与+915G/C多态性位点存在连锁不平衡,两者构成的单倍型C-G是EH危险性因素.     

新疆柯尔克孜族过氧化物酶体增殖物激活受体基因单核苷酸多态性

目的:分析柯尔克孜族健康人群过氧化物酶体增殖物激活受体基因(PPARG)的31个单核苷酸多态性(SNP)位点的遗传多态性;方法:利用Hap Map软件筛选31个SNPs位点,利用质谱检测技术进行多态性检测并根据质谱峰图判读样本目标位点基因型,利用χ~2检验确定筛选的SNP位点是否符合Hardy-Weinberg平衡定律并分析柯尔克孜族与其他民族间基因型和等位基因频率差异。结果:在31个SNP位点中,23个位点的最小等位基因频率MAF≥0.05具有多态性;在23个SNPs中rs1175540、rs17036242、rs2881654、rs2959273、rs2972162、rs4135275、rs709151、rs9310401、rs1801282位点在柯尔克孜族和维吾尔族人群间基因型和等位基因分布频率差异均有统计学意义;rs2292101、rs3856806、rs7626560位点在柯尔克孜族和北京汉族人群、犹他州居民、伊巴丹尼日利亚人群间基因型频率差异有统计学意义;rs3856806、rs4135275、rs6782475、rs7626560位点在柯尔克孜族和北京汉族人群、犹他州居民、伊巴丹尼日利亚人群间等位基因频率差异有统计学意义。结论:PPARG基因23个SNP位点多态性在新疆柯尔克孜人群和不同种族问差异具有统计学意义,这种差异可能是导致某些疾病在不同种族间的发现率和临床表现存在显著不同的因素之一。     

北方汉族2型糖尿病大血管并发症与甘露糖结合凝集素2基因及蛋白激酶C-β1基因的相关性分析

目的 探讨甘露糖结合凝集素2(mannosC-binding lectin 2,MBL2)基因rsl800450、rsl800451、rsll003125位点及蛋白激酶C-β1(protein kinase C-β1,PRKC-β1)基因rs3700106、rs2575390此5个位点的多态性及其单倍型与中国北方汉族人群2型糖尿病(type 2 diabetes mellitus,T2DM)大血管并发症(macrovascular complications,MA)的关系.方法 收集318例北方汉族了2DM患者和448名血糖正常健康对照,应用多重SNaPshot技术对病例组和无对照组的上述5个位点多态性进行检测,应用Haploview软件对5个位点进行连锁不平衡分析和单倍型分析,采用相加模型研究基因变异与环境之间交互作用对MA的影响.结果 与血糖正常的对照组相比,MA患者中心血管病变组和周围血管病变组在rs11003125多态位点上基因型频率差异均有统计学意义,户值分别为0.024和0.004,等位基因频率差异也均有统计学意义,P值分别为0.014和0.001;与无MA的72DM患者相比,周围血管病变组在rs11003125位点上的等位基因频率差异有统计学意义(P=0.031);其它位点基因型和等位基因频率在3种大血管病变组与对照组和无MA组间的分布差异均无统计学意义.单倍型分析结果显示无论与对照组还是无MA组相比,同时携带rs1800450位点G等位基因和rs11003125位点C等位基因的研究对象患MA的风险明显增高.结论 MBL2基因启动子rs11003125多态与T2DM患者MA可能相关,携带rs1800450位点G等位基因以及rs11003125位点C等位基因可能是中国北方汉族T2DM患者发生MA的危险因素.Rs11003125位点(GC+CC)变异与高血压、糖尿病肾病、糖尿病神经病变及视网膜病变在致MA的过程中可能存在正相加交互作用.     

The Association of Mitofusion-2 Gene Polymorphisms with Susceptibility of Essential Hypertension in Northern Han Chinese Population

Background: Mitofusion-2 (Mfn2) played an important role in regulating vascular smooth muscle cells proliferation, insulin resistance and endoplasmic reticulum stress, which were found to be involved in the development of hypertension. So we inferred that the Mfn2 gene may participate in the pathogenesis of hypertension. The aim of this study was to determine whether common single nucleotide polymorphisms (SNPs) in Mfn2 gene were associated with essential hypertension (EH) in northern Han Chinese.Methods: We genotyped 6 tagging SNPs of Mfn2 gene (rs2336384, rs2295281, rs17037564, rs2236057, rs2236058 and rs3766741) with the TaqMan assay in 626 hypertensive patients and 618 controls.Results: Logistic regression analysis indicated that CC+CA genotype of rs2336384 and AA+AG genotype of rs2236057 were significantly associated with increased risk of EH (OR=1.617, P=0.005; OR=1.418, P=0.031, respectively). GG genotype of rs2236058 and GG+CG genotype of rs3766741 were found to be significantly associated with decreased risk of EH (OR=0.662, P=0.023; OR=0.639, P=0.024).When stratified by gender, for rs2336384, rs2236057 and rs2236058, significant association was observed in males, but not in females. Haplotype analysis indicated that the CCAACC haplotype was positively correlated with EH and there was a negative correlation between ACAGGG haplotype and EH.Conclusions: This study demonstrated that Mfn2 gene polymorphisms were associated with essential hypertension in northern Han Chinese population, especially in male subjects.     

SH2B3基因标签单核苷酸多态性与汉族原发性高血压的关系

目的探讨SH2B衔接蛋白3(SH2B3)基因标签单核苷酸多态(SNPs)与汉族原发性高血压(EH)的关系。方法用聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP),对1 020例汉族人(EH患者和对照者各510例)SH2B3基因6个标签SNPs(rs7309325、rs11065898、rs10849947、rs2239196、rs2238154和rs739496)的多态性进行检测,运用遗传模型分析该基因与汉族EH的相关性。结果 rs2239196位点基因型和等位基因在EH组和对照组间的频率分布均具有显著性差异(Bonfferoni校正P0.05),Logistic回归分析结果显示T等位基因携带者的患病风险显著升高(OR=2.59,95%CI 1.36~4.96,Bonfferoni校正P0.05)。结论 SH2B3基因rs2239196位点T等位基因可能是汉族EH发生的危险因子。     

Association of single nucleotide polymorphisms of LEPR gene with essential hypertension among ethnic Mongolian and Han Chinese from Inner Mongolia regionCSCD

Objective: To assess the association of single nucleotide polymorphisms (SNPs) of leptin receptor (LEPR) gene with essential hypertension (EH) and body mass index (BMI) among ethnic Mongolian and Han Chinese from Inner Mongolia region. Methods: In total 411 Han Chinese patients with EH and 480 healthy controls, together with 658 Mongolian patients with EH and 403 healthy controls, were collected. The SNPs of the LEPR gene were determined with ligase detection reaction (LDR). Logistic regression was used to analyze the association of the polymorphisms of each locus with EH and BMI. MDR software was used to analyze the interaction between above loci and environmental factors. Results: Genotypic frequencies of LEPR gene rs7555955, rsll37100 and rsll37101 loci had differed significantly among ethnic Hans with EH and the control group (All P <0. 05). While those of rs7555955, rsl805094, rsll37100, rsll579567, rsl805134 and rs6669354 loci had differed significantly among ethnic Mongolians with EH and the control group (All P<0. 05). After adjustment for confounders, logistic regression analysis indicated that age(Oi=2. 97, 95%CJ: 1. 94-3. 99), BMI (Ofl = 3. 93, 95%CI:2. 91-5. 96), and rsll37101 (AA) (Oi=3. 96, 95%CI-.l. 32-11. 90) were independent risk factors for EH among ethnic Hans, while age (Oi=2. 99, 95%C7:2. 98-4. 57), BMI (Oi = 3. 03, 95%CI-. 1. 05-1. 27), rs7555955 (AG, AA) (OR = 12.12, 95%CI:2.80-52.43) OP = 6.35, 95%CI: 1. 44-27. 94), and rs7555955 (GG) were independent risk factors for EH among ethnic Mongolians (P <0. 05). Conclusion: Age and BMI are independent risk factors for EH in both ethnic Han and Mongolian Chinese. rsll37101 locus is associated with EH among ethnic Hans, while rs7555955 locus is associated with EH among ethnic Mongolians. © 2018 MeDitorial Ltd. All rights reserved.     

谷胱甘肽-S-转移酶M3基因-63A/C多态性与原发性高血压的相关性

目的研究谷胱甘肽-S-转移酶(glutathione S-transferase M3,GSTM3)基因-63A/C多态性在中国北方汉族中的分布及其与原发性高血压(essential hypertension,EH)的关联。方法应用聚合酶链反应-限制性片段长度多态性技术,对汉族234例EH患者及328名正常人GSTM3基因-63A/C位点多态性进行基因分型,随机选择部分基因型样品进行DNA测序验证。结果GSTM3基因-63A/C位点基因型分布在EH和对照组均符合Hardy-Weinberg遗传平衡。EH组CC基因型频率(6%)显著高于对照组(1.8%)(P<0.05),Logistic回归分析显示CC基因型是EH发生的一项独立危险因素(OR=3.447,95%CI:1.19～7.63;P=0.04)。结论GSTM3基因-63A/C多态性与EH相关,C等位基因可能是中国北方汉族人群EH的易感性标志。     

The association between endothelial nitric oxide synthase gene G894T polymorphism and hypertension in Han Chinese: a case-control study and an updated meta-analysis

Background: The G894T (rs1799983) polymorphism in endothelial nitric oxide synthase (eNOS/NOS3) gene has been implicated in susceptibility to essential hypertension (EH) in some studies, but no clear consensus has been reached in the Chinese population.

Aims: This study aimed to investigate the association of the G894T polymorphism and EH in Han Chinese.

Subjects and methods: First, a case-control study was performed involving 1525 subjects in northern Han Chinese to study the association between G894T variants and EH and then a meta-analysis was conducted of all available studies in Han Chinese. A total of 25 studies comprising 13?443 subjects were finally included in this meta-analysis.

Results: The present case-control study failed to show significant association of G894T variant with EH in northern Han Chinese. The subsequent meta-analysis showed that this polymorphism might be associated with EH in Han Chinese (p?p?p?=?0.12, OR?=?1.16). The meta-regression analysis suggested that the geographic difference of subjects was related to heterogeneity (p?=?0.029).

Conclusions: The relationship between the G894T polymorphism and hypertension in Han Chinese may be attributed to the difference in geographic background of subjects. It is necessary to carry out further research with a large sample size and focusing on gene–environment interactions.     

Evidence for Association of Polymorphisms in CYP2J2 and Susceptibility to Essential Hypertension

Objective Evidence from animal models and human studies suggests that CYP2J2 plays a mechanistic role in the development of hypertension. The present study aims to investigate the potential genetic contribution of the CYP2J2 gene to the etiology of essential hypertension (EH) and individual blood pressure.
Methods We selected eight polymorphisms in/or around the CYP2J2 gene and performed a case-control association study involving 841 Han Chinese subjects, including 415 unrelated hypertensives and 426 age-, gender- and area-matched normotensives.
Results Three functionally identified variants ( CYP2J2  *2, *7 and CYP2J2  *8) and SNP rs11572182 represented rare polymorphisms in Han Chinese. However, the difference in rs1155002 genotype distribution between hypertensive and healthy subjects was close to significance (P = 0.06) in the whole sample. Interestingly, significant evidence for an association with rs1155002 was found in females when stratified by gender. In females, the TT homozygote of rs1155002 seems to be a risk factor for hypertension (p = 0.014). In addition, ANOVA analysis suggested TT carriers had significantly higher systolic blood pressure (p = 0.016). The genotype frequencies for rs10493270, rs1180273 and rs1324491 revealed no statistically significant differences. Likewise, four-marker haplotype frequencies showed no significant differences between cases and controls.
Conclusion Our data provide strong evidence that the CYP2J2 gene is a susceptibility factor for essential hypertension, especially in females, and influences individual systolic blood pressure in the Chinese Han population.     

The Association between the Polymorphisms in a Sodium Channel Gene SCN7A and Essential Hypertension: A Case‐Control Study in the Northern Han Chinese

Na_x, an α‐subunit of the sodium channel encoded by the SCN7A gene, has been deemed to be a sensor of the concentration of sodium in the brain and may be involved in salt intake behavior. We inferred that Na_x/SCN7A may participate in the regulation of blood pressure and the pathogenesis of essential hypertension (EH). The present case‐control study involving 615 hypertensives and 617 normotensives was performed to investigate the association between SCN7A polymorphisms and EH in the Northern Han Chinese population. The three common single nucleotide polymorphisms (SNPs) (rs3791251, rs6738031, rs7565062) in the exons of SCN7A were genotyped with the TaqMan assay. Significant association between SNP rs7565062 and EH was found under the addictive and dominant genetic models (P = 0.024, OR = 1.283, 95%CI [1.033–1.592]; P = 0.013, OR = 1.203, 95%CI [1.040–1.392]; respectively). The three SNPs were in close pair‐wise linkage disequilibrium with each other and the haplotype analyses indicated that haplotype G–A–T was significantly associated with increased risk of EH (P = 0.023, OR = 1.290). In conclusion, our data showed that SNP rs7565062 of SCN7A was significantly associated with EH and the allele T of rs7565062 or the related haplotype G–A–T will be a genetic risk factor for EH in the Northern Han Chinese population.     

SA基因与中国汉族人群高血压病的关系

目的 探讨SA基因座是否与中国汉族人群高血压病连锁,以及SA基因多态性与中国汉族人群高血压病的关系。方法 应用MF－PCR－SSCP技术研究SA基因座微卫星的频率分布特征;以SA基因座微卫星为遗传标记,通过状态一致性受累同胞对连锁分析方法探讨SA基因座是否与高血压病连锁,运用PCR－SSCP－银染技术筛查SA基因变异体,再经测序证实,然后通过关联研究明确这种变异是否与高血压病有关。结果 （1）D16S3046、D16S3136和D16S3068多态信息量（PIC）分别为0．86、0．82和0．80,杂合度（H）分别为0．88,0．71和0．77,表明中国汉族人群SA基因座微卫星的频率分布具有高度多态性;（2）SA基因座与中国汉族人群高血压病无链关系,微卫星D16S3046、D16S3136和D16S3068连锁分析t值分别为0．972、0．622和0．236,P值分别为0．384、0．543和0．871;（3）SA基因座存在C→置换,但各基因型和等位基因的频率分布在有高血压病家族史的高血压病患者和无高血压病家族史的血压正常人之间差异无显著性,前者χ^2=0．296,P＞0．05。结论 SA基因与中国汉族人群高血压病无关,SA基因可能不是中国汉族人群高血压病的易感基因。     

血管紧张素原基因的六种单核苷酸多态与原发性高血压的相关性

目的　研究血管紧张素原 (angiotensinogen,AGT)基因 6个位点的单核苷酸多态及其构成的单倍型与中国汉族人原发性高血压的相关性。方法　采用多重SNa Pshot反应 ,在 185例原发性高血压患者和185名健康对照者中 ,对 AGT基因启动子区域的 G- 2 17A、G- 15 2 A、A- 2 0 C、G- 6 A及第 2外显子的T174 M和 M2 35 T多态进行基因分型。结果　 6种单核苷酸多态的基因型分布及其等位基因频率在原发性高血压组和对照组中差异无显著性 (P>0 .0 5 )。单倍型分析提示由 - 15 2 A,- 2 0 C,- 6 A和 2 35 T等位基因构成的 H4单倍型在原发性高血压组中明显增加 ,与对照组相比差异有显著性 (P<0 .0 5 )。结论　AGT基因G- 15 2 A,A- 2 0 C,G- 6 A和 M2 35 T多态可能对中国汉族人原发性高血压的发病起了重要作用。