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。     

eNOS 基因标签单核苷酸多态性与新疆汉族原发性高血压的相关性研究

目的: 探讨内皮型一氧化氮合酶( eNOS )基因标签单核苷酸多态性(tSNP)(rs2070744、rs1800779、rs1799983、rs3918188和rs7830)与新疆汉族原发性高血压(EH)的相关性,阐明连锁不平衡(LD)模式和单体型分布特征。方法: 采取整群抽取随机抽样的方法,选取新疆沙湾县汉族346名EH患者(EH组)与385名健康者(NT组)为研究对象,进行流行病学调查和临床检查,并采集血样。运用单碱基延伸分型(SNaPshot)技术检测 eNOS 基因标签单核苷酸多态性,确定基因型。结果: (1) eNOS 基因rs3918188位点等位基因C、A在EH组和对照组中分布频率分别为485(70.1%)、207(29.9%)和497(64.5%)、273(35.5%),EH组C等位基因频率高于对照组 (P<0.05),C等位基因患病风险为A等位基因1.287倍(95%CI 1.033-1.603,P<0.05)。rs7830位点基因型CC、AC、AA在EH组及正常对照组中的分布频率分别为126(36.4%)、185(53.5%)、35(10.1%)和145(37.7%)、173(44.9%)、67(17.4%),EH组和正常对照组基因型频率分布有显著差异(χ²=9.721,P<0.01)。其它tSNP位点基因型及等位基因频率分布在EH组和对照组间无显著差异(P>0.05)。(2)除rs1800779和rs2070744位点间存在强连锁不平衡外;其它位点间不存在强连锁不平衡;单体型TAGAC在EH组和对照组中分布频率分别为183 (26.45％)和248 (32.21％),EH组低于对照组(P＜0.05);单体型TAGCC在EH组和对照组中分布频率分别为179(25.87％)和141(18.31％),EH组高于对照组(P＜0.01)。结论: eNOS rs3918188C等位基因可能是新疆汉族EH的易感因素,rs7830位点多态性可能与新疆汉族EH相关,其它tSNP可能与该民族EH不相关;除rs1800779和rs2070744位点间存在强连锁不平衡外,其它tSNP位点间不存在强连锁不平衡;tSNP构成的单体型可能与新疆汉族EH相关。     

白介素-28B基因多态性与HCV感染后转归相关性研究

目的研究白细胞介素28B(IL-28B)基因多态性与HCV感染者转归情况的关系,以期对HCV的治疗和防御提供指导。方法采用基因测序的方法分析230例慢性HCV患者的IL-28B的rs8103142基因多态性,并对患者的HCV-RNA载量进行检测。结果 HCV携带者IL-28B的rs8103142位点的TT基因型和T等位基因的比例高于健康人群(P0.05)。HCV携带者rs8103142位点的CC基因型和C等位基因的比例在低HCV RNA水平患者明显较多(P0.05);rs8103142位点TT基因型和T等位基因的比例在高HCV RNA水平患者明显较多(P0.05)。不同HCV基因型患者的基因型和等位基因分布均有明显差异(P0.05)。接受治疗后为SVR患者的rs8103142位点的CC基因型和C等位基因的比例高于非SVR组患者(P0.05)。维吾尔族患者IL-28B的rs8103142位点的TT基因型和T等位基因的比例高于汉族患者(P0.05)。结论 IL-28B的rs12979860基因多态性与HCV感染者治疗后转归有一定联系,TT基因型可使携带者具有HCV的易感性,CC型基因型可增强携带者对HCV抗性,对临床HCV的预防和治疗有重要意义。     

SUMO4基因多态性与冠心病及2型糖尿病合并冠心病的关系

目的 探讨北京地区汉族人群小泛素样修饰蛋白4 (small ubiquitin-like modifier 4,SUMO4)基因多态性与冠状动脉粥样硬化性心脏病(coronary artery disease,CAD)及2型糖尿病(type 2 diabetes mellitus,T2DM)合并CAD的关系.方法 采用病例对照设计,入选369例单纯CAD患者(CAD组)、189例2型糖尿病合并CAD患者(T2DM+ CAD组)及500名健康个体(对照组).应用聚合酶链反应-高分辨熔解曲线技术结合测序验证法,检测SUMO4基因rs237025、rs237024及rs600739 3个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点的基因型与等位基因在3组间的分布,并通过分层分析比较SNPs不同基因型携带者的临床相关危险因素的差异.结果 3个SNPs的等位基因和基因型在3组间的分布差异无统计学意义(P＞0.05);通过分层分析,在T2DM+CAD组发现rs237025各基因型携带者的甘油三酯水平、rs600739各基因型携带者的体重指数水平的差异有统计学意义(P值分别为0.020和0.049),但组间多重比较仅发现rs237025的GG基因型携带者较GA及AA基因型携带者具有更高的甘油三酯水平(P＜0.01).结论 SUMO4基因多态性可能与北京地区汉族人群伴或不伴T2DM的CAD易感性无关.     

TBX21基因多态性与类风湿关节炎相关性的研究

目的:研究TBX21基因单核苷酸多态性(SNPs)与中国汉族人群类风湿性关节炎(RA)的关系。方法:采用单碱基延伸法(SBE)检测288例RA患者和288名正常健康者TBX21基因的5个SNPs:rs4794067、rs2240017、rs17250932、rs2074190和rs12721470的基因型。结果:5个SNP位点的基因型均符合Hardy-Weinberg平衡(P0.05)。rs12721470位点的基因型频率和等位基因频率在RA组和对照组间的差别具有统计学意义。rs4794067位点的基因型频率在RA组和对照组间无统计学差异,而等位基因频率在RA组和对照组间的差异则具有统计学意义(P0.05)。rs17250932、rs2240017和rs2074190基因型及等位基因频率在RA组和对照组间无统计学意义(P0.05)。结论:TBX21基因单核酸多态性rs12721470与中国汉人群类风湿关节炎是显著相关联的。     

G蛋白、AC、PDE和CREB SNPs与双相障碍的关联分析

目的:探讨G蛋白、腺苷酸环化酶(AC)、磷酸二酯酶(PDE)和cAMP反应元件结合蛋白(CREB)SNPs与双相障碍的关联分析。方法:①选择符合双相障碍诊断标准的患者84例(其中双相-Ⅰ型55例,双相-Ⅱ型29例),在同地区选择91名与之相匹配的健康人群,分别比较基因型、等位基因分布频率差异,同时探讨上述基因是否与双相障碍存在关联;②采用连接酶反应技术(LDR),检测GNβ3rs5443、ADCY9rs2230739 PDE1Ars1549870和CREB1rs2551638的4个单核苷酸的多态性。结果:病例组与对照组SNPs基因型频率和等位基因频率比较发现,rs5443、rs2230739、s1549870的基因型和等位基因比较差异均无显著性意义(P0.05)。另外,不同亚型间SNPs基因型和等位基因分布比较:两组之间,rs5443、rs2230739和rs1549870的基因型分布频率和等位基因频率未见存在明显差异(P0.05)。病例组双相-Ⅰ型与双相-Ⅱ型3个SNPs基因型和等位基因分布比较,也未见明显组间差异(P0.05)。结论:①没有发现GNβ3rs5443、ADCY9rs2230739、PDE1Ars1549870这3个SNPs与双相障碍存在关联的直接证据;②CREB1rs2551638位点在汉族人群中不存在多态性。     

内质网氨基肽酶-1基因(ERAP1)多态性与闽南地区汉族人群强直性脊柱炎关联性研究

本研究探讨内质网氨基肽酶-1基因(endoplasmic reticulum aminopeptidase 1,ERAP1)单核苷酸多态性与闽南地区汉族人群强直性脊柱炎(ankylosing spondylitis,AS)的相关性。选取经纽约诊断标准确诊的闽南地区汉族149例强直性脊柱炎患者(AS组)与150例健康人群(对照组),应用SNaPshot单碱基延伸反应测定所有研究对象ERAP1的10个SNP位点(rs26653、rs7711564、rs27980、rs30187、rs2287987、rs10050860、rs27529、rs17482078、rs27038、rs27044)基因型。结果显示,ERAP1的3个SNP位点rs27044(OR=1.324,P=0.001)、rs30187(OR=1.224,P=0.011)、rs27980(OR=1.220,P=0.005)位点基因型在闽南地区汉族人群AS组和正常对照组之间比较具有显著性差异(P0.05),其罕见等位基因是AS发病的危险因素,rs26653、rs7711564、rs2287987、rs10050860、rs27529、rs17482078、rs27038等SNP位点两组之间比较无统计学差异(P0.05)。本研究表明ERAP1基因单核苷酸多态性rs30187、rs27044、rs27980与闽南地区汉族人群强直性脊柱炎相关,进一步证实了该rs27044位点的等位基因(G)、rs30187位点的等位基因(T)、rs27980位点的等位基因(C)基因是强直性脊柱炎的易感基因。     

CSPG2和HSPG2基因单核苷酸多态性与中国汉族人颅内动脉瘤的相关性研究

目的 分析CSPG2和HSPG2基因单核苷酸多态性(single nucleotide polymorphism,SNP)与中国汉族散发颅内动脉瘤的相关性.方法 采用病例-对照关联研究方法,收集颅内动脉瘤患者537例以及年龄和性别匹配的正常对照1071名的外周血样各5 mL并提取基因DNA.通过聚合酶链式反应扩增目的DNA,用单碱基延伸(SNaPshot)法进行SNP分型.选取文献报道的CSPG2和HSPG2基因的两个标签SNPs位点rs251124和rs3767137,分析其与汉族散发颅内动脉瘤发病的关联性.结果 CSPG2和HSPG2基因的两个标签SNPs位点rs251124和rs3767137的基因型均满足Hardy-Weinberg平衡.CSPG2rs251124的等位基因频率在患者组与对照组之间差异无统计学意义(P=0.22);HSPG2 rs3767137的等位基因频率在两组之间亦差异无统计学意义(P=0.26),但其相应的OR值大于1(OR=1.12;95％CI=0.92～1.37).患者组与对照组rs251124、rs3767137的基因型频率均差异无统计学意义(P=0.46,0.53).结论 未发现CSPG2和HSPG2基因rs251124、rs3767137 SNPs与中国人颅内动脉瘤发病的相关性.     

CDKAL1基因rs4712523多态性与内蒙古地区汉族人群2型糖尿病相关

目的 研究内蒙古地区汉族人群CDKAL1基因rs4712523单核苷酸多态性(SNP)的等位基因和基因型频率分布与2型糖尿病(T2DM)的相关性.方法 采用等位基因特异性聚合酶链式反应(AS-PCR),对382例内蒙古地区汉族人(其中T2DM组192例,对照组190例)rs4712523进行基因分型.结果 T2DM组中rs4712523的G等位基因频率和GG基因型频率分别为47.4％和6.3％,均显著高于对照组的35.3％和3.2％(P＜0.05).G等位基因携带者患T2DM的风险是A等位基因的1.654倍(OR=1.654,95％ CI=1.237-2.212).结论 CDKAL1基因rs4712523多态性位点的G等位基因可能是内蒙古地区汉族人T2 DM的易感基因之一.     

2型糖尿病患者肝脂肪酶基因标签单核苷酸多态性与血脂水平分析

观察汉族人群肝脂肪酶(HL)基因2个标签单核苷酸多态性(SNP)与2型糖尿病(T2DM)及血脂代谢的相关性.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HL基因rs 12462668和rs10426971多态性.用全自动生化分析仪检测CHO、TG、HDL-C、LDL-C、载脂蛋白Al( ApoAl)及...     

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.     

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.     

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.     

Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population

A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender and diabetes status. In the study, we confirmed the association of SNP rs12696304 and rs16847897 near TERC with LTL in the Chinese Han population (P ～ 4.5 × 10(-3) and 9.5 × 10(-5), respectively). Each copy of the major allele of rs12696304 and rs16847897 was associated with a shorter mean telomere length of 0.024 and 0.031 T/S respectively, which is equivalent to about 3 and 4 years of average age-related telomere attrition. Our short report confirmed the effects of SNPs near TERC on LTL in the Chinese Han population for the first time.     

Association study of polymorphisms in miRNAs with T2DM in Chinese population

Accumulated evidence indicates that microRNA (miRNA or miR) is involved in the development of type 2 diabetes (T2DM). Several studies have shown that single nucleotide polymorphisms (SNPs) located in miRNAs are associated with T2DM in Caucasian populations. The association studies of miRNA''s SNPs with T2DM in Asian are rarely reported, and there are distinct genetic differences between Caucasian and Asian populations. The focus of this study, therefore, is the association of T2DM with five SNPs (rs895819 in miR-27a, rs531564 in miR-124a, rs11888095 in miR-128a, rs3820455 in miR-194a and rs2910164 in miR-146a) located in five miRNAs in a Han Chinese population. A total of 738 subjects with T2DM and 610 non-diabetic subjects were genotyped using the TaqMan method. Next, the associations between the five SNPs with T2DM and individual metabolic traits were evaluated. Our data showed that the C allele of rs531564 in miR-124a may protect against T2DM (P=0.009, OR=0.758; 95%CI: 0.616-0.933). Conversely, the C allele of rs2910164 in miR-146a may increase the risk of developing T2DM (P<0.001, OR=1.459; 95%CI: 1.244-1.712). However, these five SNPs did not exhibit significant associations with individual metabolic traits in either the T2DM or non-diabetic groups. Our results revealed that genetic variations in miRNAs were associated with T2DM susceptibility in a Han Chinese population, and these results highlight the need to study the functional effects of these variants in miRNAs on the risk of developing T2DM.     

AQP7和AQP9基因多态性与中国汉族人群2型糖尿病的相关性研究CSCD

目的探讨水通道蛋白7(aquaporin 7, AQP7)以及水通道蛋白9(aquaporin 9, AQP9)基因单核苷酸多态性(single nucleotide polymorphism, SNP)与中国汉族人群患2型糖尿病(type 2 diabetes mellitus, T2DM)的相关性。方法随机纳入1194例T2DM个体和1274例非糖尿病个体(non-diabetic, NDM)进行对照研究, 采用MassArray质谱基因分型方法对3个SNP位点(AQP7基因rs3758269、AQP9基因rs16939881和rs57139208)进行基因分型。评估以上3个SNP位点与T2DM的相关性;探讨NDM组SNP位点处不同基因型与糖脂代谢指标的关联。结果 AQP7基因rs3758269、AQP9基因rs16939881和rs57139208的等位基因频率及基因型频率在T2DM组和NDM组中的分布无统计学差异(P > 0.05);且分析结果显示不同遗传模式与T2DM无相关性(P > 0.05)。在NDM组中, AQP7基因rs3758269、AQP9基因rs16939881和rs57139208的不同基因型与糖脂代谢指标无相关性(P > 0.05)。结论 AQP7基因rs3758269和AQP9基因rs16939881和rs57139208与中国汉族人群T2DM遗传易感性无关。     

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。     

Association Study of ARL15 and CDH13 with T2DM in a Han Chinese Population

Several studies indicate that plasma adiponectin levels are associated with the risk of type 2 diabetes mellitus (T2DM) or T2DM risk factors in diverse populations. In addition to the adiponectin gene, several other genes have been postulated to influence plasma adiponectin levels. In this study, we investigated two single nucleotide polymorphisms (SNPs), rs4311394 and rs4783244, located intronically in the ADP-ribosylation factor-like protein 15 (ARL15) and the T-cadherin (CDH13) genes, respectively. These SNPs were detected in a Han Chinese population using a TaqMan assay and evaluated for association with T2DM as well as with individual metabolic traits. Allele frequencies for rs4311394 were significantly different in T2DM and nondiabetes (NDM) groups (χ² = 4.49, P = 0.034). However, neither allele nor genotype frequencies for rs4783244 were associated with T2DM (χ² = 0.33, P = 0.56 and χ² = 2.35, P = 0.31 respectively). The SNPs did not exhibit significant association with individual metabolic traits in the T2DM and NDM groups. Our results indicated that the G allele of the rs4311394 might be a susceptibility factor for T2DM in the Han Chinese population (odds ratio: 1.20; 95% confidence interval: 1.01-1.41).