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。     

巨噬细胞移动抑制因子基因rs1007888位点单核苷酸多态性与哈萨克族 冠状动脉粥样硬化性心脏病发病的相关性

背景：有研究表明巨噬细胞移动抑制因子是具有多种生物活性的细胞因子,在机体的炎症和免疫反应中起重要作用。巨噬细胞移动抑制因子rs1007888已被报道与多种炎症性疾病相关,但其与哈萨克族冠状动脉粥样硬化性心脏(冠心病)病易感性是否具有关联性少见报道。 目的：探讨巨噬细胞移动抑制因子rs1007888位点基因多态性与新疆哈萨克族人群冠心病之间的相关性。 方法：选择2012年6月至2014年4月于新疆医科大学附属第一医院心脏中心入院,经皮冠状动脉造影检查确诊的哈萨克族冠心病患者230例为冠心病组,以同期冠脉造影阴性、排除冠心病诊断的478例哈萨克族为健康对照组。采用实时荧光定量PCR法对所有纳入对象巨噬细胞移动抑制因子rs1007888位点基因多态性进行检测,比较两组间巨噬细胞移动抑制因子基因多态性频率分布的差异。 结果与结论：冠心病组与对照组基因型分布符合Hardy-Weinberg平衡(P > 0.05),两组的巨噬细胞移动抑制因子rs1007888位点基因型、等位基因频率均差异无显著性意义(P > 0.05)。结果证实,rs1007888位点基因多态性与新疆维吾尔自治区哈萨克族冠心病发病无显著相关性,该位点突变可能不是哈萨克族人群冠心病的易感因素。  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

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.     

神经前体细胞表达发育调控样基因rs4149601多态性与新疆哈萨克族人群中心性肥胖的关联研究

目的 研究神经前体细胞表达发育调控样基因rs4149601多态性与新疆哈萨克族人群中心性肥胖的相关性.方法 采取以人群为基础的横断面病例-对照研究方法,采用TaqMan聚合酶链反应对新疆哈萨克族856名自然人群(男性364名、女性492名;其中肥胖478例、对照378名)的rs4149601多态性进行分型,分析其与新疆哈萨克族人群肥胖的相关性.结果 共有853名的基因型分型成功,在总体女性新疆哈萨克族自然人群中,rs414960l多态性的基因型、等位基因在肥胖组及对照组分布差异有统计学意义(P＜0.05).在校正了年龄、吸烟、饮洒和性别等影响因素后,Logistics回归分析显示GG基因型仍与新疆哈萨克族人群中心性肥胖相关(OR=1.479,95%CI:1.103～1.983,P=0.009);协方差分析结果提示携带GG基因型者的腰围高于AA携带者+AG携带者(P=0.028).结论 神经前体细胞表达发育调控样基因的rs4149601多态性与新疆哈萨克族人群中心性肥胖相关,GG基因型可能是哈萨克族人群中心性肥胖的易感因素.     

固醇调节元件结合蛋白1c基因多态性rs2297508、rs11868035与甘肃汉族、东乡族人群2型糖尿病的相关性

目的 探讨固醇调节元件结合蛋白1c(sterol regulatory element binding protein-lc,SREBP-lc)基因多态性rs2297508、rs11868035在甘肃汉族、东乡族人群中的分布及其与2型糖尿病(type 2diabetes mellitus,T2DM)的相关性.方法 选择汉族2型糖尿病患者342例以及正常对照343人,东乡族2型糖尿病患者218例以及正常对照238人,采用聚合酶链反应-变性高效液相色谱法检测SREBP-1c基因型,采用氧化酶法或放免法测定血糖、胰岛素及血脂水平.采用卡方检验进行统计学分析.结果 SREBP-lc基因多态位点rs2297508、rs11868035在汉族和东乡族正常对照者中的基因型和等位基因频率分布差异无统计学意义(P＞0.05).上述位点在汉族、东乡族人群2型糖尿病患者C等位基因和CC基因型频率均明显高于对照组,差异均有统计学意义(P＜0.01).在汉族对照组中,rs2297508的C等位基因携带者的低密度脂蛋白胆固醇水平明显高于GG者,其差异有统计学意义(P＜o.05).在东乡族对照组中,CC基因型的低密度脂蛋白胆固醇水平明显高于GG者,其差异有统计学意义(P＜0.05).结论 SREBP-lc基因多态性rs2297508、rs11868035在甘肃汉族和东乡族人群中均与2型糖尿病发病存在关联.C等位基因可能是罹患2型糖尿病的危险因素之一.上述多态性在汉族和东乡族人群中的分布并无差异.SREBP-le基因多态性rs2297508可能与低密度脂蛋白胆固醇升高有关.     

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。     

PCSK9基因rs2479409位点多态性与认知障碍相关

目的探讨前蛋白转化酶枯草溶菌素9(PCSK9)基因rs2479409位点多态性与认知功能障碍的相关性。方法在中国江苏省如皋县开展的以人群为基础的病例对照研究中,共纳入了1 707例年龄70~84岁的研究对象,使用改良长谷川痴呆量表(HDS-R)评价该人群认知功能,并检测了该人群中PCSK9基因rs2479409位点单核苷酸多态性情况。结果该人群PCSK9基因rs2479409多态性主要以GG和AG基因型存在。认知障碍组和对照组在rs2479409位点的等位基因频率、基因型频率分布有差异(P0.05)。A等位基因为认知障碍保护性因素,GG基因型相对于AA基因型1.66倍增加认知障碍发生风险(OR=1.66,95%CI 1.16~2.36,P0.01),调整相关混杂因素后仍有统计学差异(P0.05)。结论 PCSK9基因rs2479409位点多态性与认知障碍相关。     

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。     

载脂蛋白E基因启动子区多态性分布在新疆哈汉民族冠心病患者之间差异性研究

目的:研究新疆地区哈、汉民族冠心病患者载脂蛋白E基因启动子区rs405509(G-T)、rs449647(A-T)、rs7259620(G-A)位点多态性的分布在两民族之间是否存在差异。方法:纳入病例201例,利用酚-氯仿法抽提提取DNA,再将PCR产物进行纯化。SNaPshot多重单碱基延伸反应纯化后得到的延伸产物在ABI3130XL基因分析仪上进行测序。结果:新疆地区哈萨克族与汉族患者中载脂蛋白E基因启动子区rs449647(A-T)位点基因型及等位基因在两民族之间差别具有统计学意义(P<0.05),rs405509(G-T)位点及rs7259620(G-A)位点基因型及等位基因在两民族之间差异均无统计学意义(P>0.05)。结论:载脂蛋白E启动子区rs449647(A-T)位点基因型及等位基因多态性分布在新疆地区哈、汉冠心病病人中有统计学差异,其余两个位点多态性在哈、汉民族间的分布无统计学差异。     

Relationship between the single nucleotide polymorphisms of β2-adrenergic receptor 5’-regulatory region and essential hypertension in Chinese Kazakh ethnic minority group

Objective: To study the correlation of β₂-AR gene 5’-regulatory region SNPs and essential hypertension (EH) in Chinese Kazakh ethnic minority group. Methods: The Sequenom MassArray^® SNP detection technology was used to detect β₂-AR gene 5’-regulatory region SNPs in 150 Xinjiang Kazakh EH patients and 150 controls. Biochemical analyzer was used to detect lipid and other related biochemical parameters. SHEsis and other software were used to analyze linkage disequilibrium and haplotype. Results: Six loci rs205304 (-1023G/A), rs17108803 (-893T/G), rs12654778 (-654G/A), rs11168070 (-468C/G), rs11959427 (-367C/T) and rs2895795 (-1429T/A) polymorphisms of β₂-AR gene 5’-regulatory region were found in the Xinjiang Kazakh populations. While, there was no significant difference between EH group and NH in genotypes and allele frequency of rs2053044, rs12654778, rs2895795, rs17108803 and rs11959427 (P>0.05). However; significant differences were detected of rs11168070 genotypes and allele frequency in two groups (P<0.05). Analysis of the linkage disequilibrium and haplotype in Kazakh population, there is a strong linkage disequilibrium of rs11168070, rs2053044, rs2895795 gene polymorphism in the EH group, and rs11168070, rs12654778, rs17108803 gene polymorphism in controls. Frequency of haplotype GTCCAT, GACTGT and ATGCGT in EH group was higher (P<0.05), while frequency of ATCTGT, ATGTGT, GTCCGT, GTCTAT, GACCAT and GTCTGT in the EH group was significantly lower than the control (P<0.05). Conclusions: β₂-AR gene 5’-regulatory region of rs11168070, rs2053044, rs17108803, rs12654778, rs11959427 and rs2895795 genetic polymorphism exists in Kazakh. Among them, rs11168070 locus genotype and allele frequency distribution in the two groups are significant differences. In six polymorphic loci, there is a strong linkage disequilibrium, which haplotypes GTCCAT, GACTGT, ATGCGT are risk factors of EH, and the ATCTGT, ATGTGT, GTCCGT, GTCTAT, GACCAT, GTCTGT are protective factors.     

新疆哈萨克族隔离群醛固酮合成酶基因多态性与原发性高血压的关联性

目的探讨哈萨克族人群醛固酮合成酶基因CYP11B2T(-344)C多态性与原发性高血压的关联性。方法用聚合酶链反应、限制性内切酶方法检测了新疆巴里坤县哈萨克族186例原发性高血压患者和168名正常人群CYP11B2基因T(-344)C多态性。结果哈萨克族正常人群及高血压患者的CYP11B2基因T(-344)C多态CC、CT、TT基因型频率分布分别为0.12、0.61、0.27和0.20、0.50、0.30,C和T等位基因分布频率分别为0.43、0.57和0.45、0.55,符合Hardy-Weinberg平衡。群体相关分析结果表明CYP11B2基因的C及T等位基因分布在高血压病组及正常人群差异无显著性(χ2=0.380,P=0.537);基因型频率之间差异无显著性(χ2=4.838,P=0.089)。然而女性高血压组CC基因型频率较正常人群高(χ2=6.104,P<0.05)。结论CYP11B2基因T(-344)C多态性可能与新疆巴里坤哈萨克族女性高血压有关。     

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.     

SLC2A4基因启动子区rs5418位点变异对基因表达的影响

目的: 研究葡萄糖转运蛋白4(SLC2A4)基因启动子区rs5418多态位点G→A变异对基因表达的影响。方法: PCR法扩增SLC2A4基因核心启动子区序列。采用基因重组、定点突变等技术,构建rs5418位点含有不同等位基因的SLC2A4基因启动子重组表达载体。脂质体转染法将重组质粒转入HEK293T细胞,采用双萤光素酶报告系统,观察携带不同等位基因的重组质粒中下游报告基因的表达活性。结果: PCR扩增获得长度为716 bp的SLC2A4基因核心启动子序列,成功构建pGL3-SLC2A4-prom(A)和pGL3-SLC2A4-prom(G)重组表达载体。双萤光素酶报告基因活性检测结果显示,携带A等位基因的载体启动下游报告基因表达的相对活性(19.49±4.41)比携带G等位基因的载体(13.04±4.45)强,两者存在显著差异(P<0.05)。结论: SLC2A4基因启动子区rs5418位点的G→A突变能显著增强启动子活性,从而影响SLC2A4基因表达活性。     

Sex-specific association of the SPTY2D1 rs7934205 polymorphism and serum lipid levels

The objective of the present study was to detect the association of the rs7934205 single nucleotide polymorphism (SNP) near the Suppressor of Ty, domain containing 1 gene (SPTY2D1) and serum lipid levels between males and females in the Mulao and Han populations. Genotyping of SPTY2D1 rs7934205 SNP was performed in 933 of Mulao and 865 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The T allele frequency was different between Mulao males and females (23.2% vs. 27.9%, P = 0.018). The genotype and allele frequencies were also different between Han males and females (P = 0.020 and P = 0.004; respectively). Serum levels of apolipoprotein (Apo) A1 in Mulao males; and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ApoA1 and ApoB in Mulao females were different between the CC and CT/TT genotypes (P < 0.05). Serum TC, ApoB levels in Han males, and ApoB levels in Han females were different between the CC and CT/TT genotypes (P < 0.05). The subjects with CT/TT genotype in both Mulao and Han males and females have more favorable lipid profiles than those with CC genotype. These findings suggest that the association between the SPTY2D1 rs7934205 SNP and serum lipid levels might have ethnic- and/or sex-specificity.     

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.     

Association between the MARS rs6782181 polymorphism and serum lipid levels

Little is known about the association between the muscle Ras (MRAS) gene rs6782181 polymorphism and serum lipid levels. The aim of the present study was to investigate the association between the MRAS rs6782181 polymorphism and serum lipid levels in the Mulao and Han populations. A total of 632 subjects of Han and 629 unrelated subjects of Mulao nationalities were randomly selected from our previous stratified randomized samples. Genotypes of the MARS rs6782181 polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism. The subjects with GG genotype had higher serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (Apo) B levels in Han, and higher serum TC and LDL-C levels in Mulao than the subjects with AA/AG genotypes (P < 0.05-0.01). Subgroup analyses showed that the subjects with GG genotype had higher TC, TG, high-density lipoprotein cholesterol (HDL-C), LDL-C, ApoAI and ApoB in Han males, lower ApoAI and the ratio of ApoAI to ApoB in Han females; and higher LDL-C levels in Mulao males but not in Mulao females than the subjects with AG/AA genotypes. The association of the MARS rs6782181 polymorphism and serum lipid levels is different between the Mulao and Han populations, or between males and females in the both ethnic groups. There may be an ethnic- and/or sex-specific association between the MRAS rs6782181 polymorphism and serum lipid levels in our study populations.