正常人与白血病患者GPI-PLD基因外显子1多态性分析

现已发现1 5 0余种蛋白质通过糖基化磷脂酰肌醇(GPI)锚定于细胞表面,包括细胞黏附分子、淋巴细胞分化抗原、肿瘤标志物等。人类造血细胞膜上的分化抗原(CD)约1 0 %是GPI锚定蛋白[1 ] ,对造血细胞的生成、分化、成熟等起着重要作用。人体中能水解GPI、释放锚定蛋白的酶只有GPI特异性磷脂酶D(GPI PLD)。不同病理状态下人血浆中GPI PLD活性改变不同[2 ] 。为探讨白血病患者外周血有核细胞GPI PLD基因是否存在单核苷酸多态性(SNP)及GPI PLD活性水平,我们对湖南地区白血病患者与正常人GPI PLD基因外显子1多态性分布情况及外…     

RhD^u、Del型的D基因外显子多态性分析

ＲｈＤ抗原是除ＡＢＯ血型系统之外最具免疫原性的红细胞抗原分子 ,在Ｒｈ血型系统中占重要地位[1] 。Ｄ抗原根据其抗原量的变化表现其抗原性的强弱 ,表型Ｄ— /Ｄ—抗原性最强 ,其次为弱Ｄ (Ｄｕ)、最弱为Ｄｅｌ型[2 ] 。既往对Ｄｕ 及Ｄｅｌ基因结构仅限于推测 ,笔者采用基因检测技术分析构成Ｄｕ、Ｄｅｌ型基因的结构 ,现报告如下。1　材料和方法1 1　Ｄｕ 标本　 5例 ,用血清学技术 2次检定 ,方法按《中国输血技术操作规程》操作[3] 。1 2　Ｄｅｌ标本　 8例 ,经血清学技术检定为Ｒｈ阴性(方法同上 )的标本再用吸收放散试验检定。采用三…     

载脂蛋白E外显子4基因多态性与Alzheimer‘s病

探讨了载脂蛋白Ｅ（ａｐｏＥ）外显子４基因多态性与Ａｌｚｈｅｉｍｅｒ‘ｓ病的关系。应用聚合酶链反应扩增ａｐｏＥ外显子４基因片段，对扩增片段用ＨｈａⅠ酶切消化后进行基因分型，并用ＤＮＡ测序技术对分型结果予以证实，Ａｌｚｈｅｉｍｅｒ’ｓ病组与年龄匹配对照组在ａｐｏＥ外显子４ε３／４基因型频率和ε４等位基因频率分布上的差异有显著性（ｘ＾２＝８．９１，Ｐ〈０．０５，Ｘ＾２＝９．４９，Ｐ〈０．０１），Ａｌｚｈ     

中国汉族群体RhD—（—）个体D基因和CED基因外显子多态性研究

Rh血型系统是继ABO血型之后临床意义最大的一个血型系统,也是最复杂的血型系统之一。最新的分子生物学研究表明,RhD阳性个体的Rh基因座位是由RHD和RHCE两个结构基因组成［1］,这两个基因均含有10个外显子,而RhD(－）个体仅有一个RHCE基因［2］。值得注意的是RhD基因结构存在种族差异,东方人、非洲黑人RhD(－)个体与高加索人种 RhD (－)个体的基因结构存在明显的差异［3,4］。笔者用聚合酶链反应-序列特异性引物（PCR-SSP）方法特异性地扩增100名中国汉族RhD（－)个体的RHD基因,以探讨中国汉族RhD(－)个体的D基因结构,并与其他民族进行比较。     

内皮型氧化亚氮合酶基因G894T、胰岛素受体基因第17外显子多态性与老年痴呆的关系研究

目的研究内皮型氧化亚氮合酶基因第7外显子G894T、胰岛素受体基因第17外显子多态性与老年痴呆的相关性。方法选取本院门诊及住院阿尔茨海默病（AD组）与血管性痴呆患者（VaD组）各50例。对照组为同期收集的健康老年人50例,抽取受试者清晨空腹静脉血5 mL,血细胞提取DNA。对受试者的内皮型氧化亚氮合酶基因G894T和胰岛素受体基因第17外显子进行基因分析。结果 AD组、VaD组与对照组的GG、GT和TT基因型分布频率分别比较,差异有显著统计学意义;AD组患者的INSR T等位基因频率高于对照组,但差异不明显（P〉0.05）。VAD组患者的INSR T等位基因频率显著高于对照组。结论内皮型氧化亚氮合酶基因G894T多态性、胰岛素受体基因第17外显子多态性与阿尔茨海默病、血管性痴呆患者具有相关性,AD和VaD存在相同的基因危险因素。     

中国人内源性高甘油三酯血症中ApoB基因第26外显子XbaI多态性分析

目的　对中国人内源性高甘油三酯血症 (hypertriglyceridemics ,HTG)中ApoB基因第 2 6外显子XbaI多态性进行分析。方法　采用聚合酶链反应和限制性片段长度多态性 (PCR RFLP)方法 ,对沈阳地区 115名HTG患者及 15 0名血脂正常健康成人ApoB基因第 2 6外显子XbaI多态性进行分析 ;同时测定血脂及载脂蛋白水平 ,分析ApoB基因XbaI多态性对血脂及载脂蛋白水平的影响。结果　正常对照组及HTG组中基因型均以X -X -为主。HTG组X +等位基因分布频率及X +X -基因型分布频率均显著高于对照组 (13.5 %vs 4 .0 % ,P <0 .0 1;2 5 .2 %vs 8.0 % ,P <0 .0 1)。HTG组中 ,X +X -基因型者TG、TC、LDL C、ApoB水平均高于X -X -基因型者 (TG、ApoB水平P <0 .0 5 ;TC、LDL C水平P <0 .0 1)。结论　ApoB基因第 2 6外显子XbaI多态性与中国人内源性高甘油三酯血症的遗传易感性有一定关联 ,X +等位基因的存在可能是中国人HTG发生的一个重要因素。     

SMPD1基因多态性与帕金森病发病关系的研究

目的分析SMPD1基因多态性与帕金森病(PD)发病的关系,为PD患者的治疗提供新的靶点。方法收集2017年6月至2019年1月该院神经内科收治的216例PD患者(PD组)和同期在本院体检的216名健康者(健康组)作为研究对象,参照SMPD1基因序列及相关文献设计引物序列,采用PCR和限制性内切酶酶切技术检测两组SMPD1基因多态性。结果 PD组rs1050228位点TT、CT、CC基因频率、等位基因T、C频率(分别为73.15%、5.56%、21.30%、76.07%、23.93%)与健康组(分别为72.22%、6.02%、21.76%、78.03%、21.97%)相比较差异均无统计学意义(P0.05);rs7951904位点的CC、CT基因频率、等位基因C、T频率(分别为99.07%、0.93%、99.64%、0.36%)与健康组(分别为99.54%、0.46%、99.81%、0.19%)相比较,差异均无统计学意义(P0.05);rs202081954位点的CC、CG基因频率、等位基因C、G频率(分别为99.07%、0.93%、99.64%、0.36%)与健康组(分别为99.54%、0.46%、99.81%、0.19%)相比较,差异均无统计学意义(P0.05);rs1050239位点的等位基因G、A频率(分别为81.43%、18.57%)与健康组(分别为91.62%、8.38%)相比较差异有统计学意义(P0.05);PD组和健康组均发现缬氨酸重复次数的多态,且PD组缬氨酸重复次数分布概率与健康组相比较,差异有统计学意义(P0.05)。结论 SMPD1基因突变型p.G508R及缬氨酸7个重复多态在PD的诊断或预防中可提供有用参考信息。     

LSM1基因多态性与江苏地区汉族人精神分裂症的关联性研究

目的探讨LSM1基因多态性与江苏地区汉族人精神分裂症的关联性。方法用连接酶检测反应PCR(LDR-PCR)单核苷酸多态性(SNP)分型技术对506例精神分裂症患者和522例健康对照者LSM1基因rs16887244、rs2843738、rs2843746 3个标签单核苷酸多态性(tgSNP)进行基因分型,比较各组间等位基因、基因型分布频率。结果与健康对照组比较,精神分裂症组rs16887244等位基因分布频率差异不显著(OR=0.992,P=0.935);rs2843738和rs2843746等位基因分布频率也无显著差异(OR分别为1.036,1.013,P均>0.05);rs16887244基因型(AA/AG/GG)、rs2843738基因型(CC/CG/GG)和rs2843746基因型(CC/CT/TT)分布频率均无显著差异(χ2分别为0.511,0.147,5.981,P均>0.05)。结论江苏地区汉族精神分裂症患者与LSM1基因rs16887244、rs2843738、rs2843746多态性不相关。     

裕固族人群IL-1基因多态性分析

IL-1是一种具有广泛生物活性的细胞因子，近年来研究发现IL-1基因多态性与其基因的转录和表达有关，也与冠心病、自身免疫性疾病等密切相关。结合临床对IL-1基因多态性进行分析，可从基因水平了解疾病个体化临床表现的相关机制，寻找更有针对性的治疗手段。本研究对IL-1（B-511、B-1470、RN）基因的多态性进行了分析。     

Association of IL-1Ra gene polymorphism, but no association of IL-1beta and IL-4 gene polymorphisms, with Kawasaki disease

The purpose of this study was to evaluate whether IL-1 beta (IL-1beta promoter and IL-1beta exon 5), IL-1 receptor antagonist (IL-1 Ra), and IL-4 (IL-4 promoter and IL-4 intron 3) gene polymorphisms act as markers of susceptibility to Kawasaki disease (KD), or of the severity of the disease. The study included 107 KD patients and 103 normal controls. Polymorphisms for cytokine genes were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for cytokine gene polymorphisms in both groups were compared. No significant difference was observed in the genotypes and allelic frequencies of cytokines between patients with coronary aneurysm and without. In addition, there was no significant association in the genotype and allelic frequencies of IL-1 beta, IL-4, and IL-6 in patients with KD. The genotype I/II for IL1-Ra and the frequency of allele II for IL1-Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD.     

蛋白酪氨酸磷酸酶-1B基因多态性与2型糖尿病的相关性研究

目的 探讨蛋白酪氨酸磷酸酶—1B(protein tyrosine phosphastase-1B,PTP—1B)基因387位编码子Pro-Leu多态性与2型糖尿病(T2DM)的关系。方法 采用多聚酶联反应—限制性片段长度多态性(PCR—RFLP)的方法对湖北地区130例2型糖尿病患者及138例正常对照者PTP—1B基因387位编码子酶切位点进行研究。结果 2型糖尿病患者和正常对照者PTP—1B基因均以PP基因型为主，其频率分别为0．94和0．96；P等位基因频率分别为0．97和0．98，差异无统计学意义(P＞0．05)。2型糖尿病患者中PTP—1B基因P387L变异与体重指数(BMI)有关，但与空腹血糖、空腹胰岛素、总胆固醇、甘油三酯等临床变量不相关。结论 未发现PTP—1B基因387位Pro-Leu多态性与中国人2型糖尿病有关。     

中国人群RhD阴性个体中D基因多态性的研究

目的 建立RHD基因分型技术，分析中国人群RhD阴性个体的RHD基因多态性分布状况。方法 设计8对特异性引物扩增RHD7个外显子(3，4，5，6，7，9，10)和内含子4，应用PCR—SSP技术，对l15例经常规血清学试验和吸收放散试验鉴定的“Rh阴性个体”，进行D基因多态性的研究。结果 l15例RhD阴性个体，用吸收放散试验检测后分成2组，一组被确认为RhD阴性表现型共88例(76．5％)，另一组是Del(放散)表现型共27例(23．5％)。应用PCR—SSP法对l15例RhD阴性个体作RHD内含于4检查，结果Del型个体都显示有RHD内含于4；对l15例中的17例进一步作RHD的7个外显子的鉴定，其中6例Del带有完整的RHD基因，ll例经吸收放散试验确认为RhD阴性表现型的个体则显示4种情况：7例全部缺失RHD基因，2例(1例ccEe和1例Ccee)带有完整的RHD基巴，1例缺失RHD的第5外显子和1例仅携带第10外显子。结论 PCR—SSP技术可用于RHD基因的研究。常规血清学鉴定的RhD阴性中存在较高比例的Del型，且有可能带有完整的RHD基因。而被吸收放散试验确认为RhD的阴性个体有可能携带RHD基因并显示出多态性，这些个体中有Rhc抗原表达，有别于献中认为全局RhC抗原表达的报告。     

肾素-血管紧张素系统基因多态与子痫前期的相关性

目的：探讨肾素-血管紧张素系统基因中血管紧张素原（ACT）基因M235T多态、血管紧张素Ⅰ转换酶（ACE）基因插入，缺失（I／D）多态和血管紧张素Ⅱ-1型受体（AT。R）基因A1166C多态与子痫前期的关系。方法：应用聚合酶链反应（vca）、限制性酶切及电泳分型等方法对45例子痫前期患者（子痫前期组）和45例非高血压妊娠妇女（对照组）的AGT基因M235T多态、ACE基因Ⅰ/D多态、AT1R基因A1166C多态性进行分析。结果：（1）AGTM235T多态的TT基因频率两组比较差异有显著性。（2）ACE基因DD、ID、Ⅱ型在两组中分布无明显差异。（3）AT1R基因A1166CAA、AC、CC型在两组中分布无明显差异。（4）子痫前期组具备TT基因型者，其合并DD基因型的95％口为1．473—31．919，合并1166C等位基因C的95％CI为1．316～18．991。结论：AGT变异基因235T与子痛前期发生有关，T等位基因可能是子痫前期的易感基因。ACE基因DD型与子痫前期的相关性限于携带有M235T等位基因的患者。携带有AT1R基因C等位基因和AGT基因TT型的妇女子痫前期发病危险升高。     

新发和复发肺结核维生素D受体基因多态性分布

目的了解维生素D受体(VDR)基因多态性在中国汉族人群新发和复发肺结核中的分布情况,为探讨其与新发、复发肺结核的相关性打下基础。方法采用病例对照研究,选择新发、复发肺结核患者和健康对照者各30例,使用SNaPshot的SNP分型技术对以上入选者的VDR基因TaqI和FokI多态性位点进行检测分析。结果VDR基因FokI位点ff多态性在肺结核和对照组分布有差异(OR=6.53,95%CI:1.26~33.9,P=0.03);TaqI和FokI位点多态性在新发和复发肺结核中的分布差异无统计学意义(P>0.05)。结论VDR基因ff多态性与中国汉族肺结核易感性有关;TaqI和FokI位点多态性在新发和复发肺结核中的分布是否存在差异有待进一步研究。     

DNA polymorphisms of the alpha 1-antitrypsin gene region in patients with chronic obstructive pulmonary disease

Alpha 1-antitrypsin (AAT) is an important part of the defence mechanism of the lung against proteolytic attack. The Z and Null mutants of the AAT gene are associated with very low or missing serum concentrations of AAT, so that for individuals with genotypes ZZ or Null there is a very high risk of developing chronic obstructive pulmonary disease (COPD). In more than 90% of the patients suffering from COPD, however, the common MM phenotype of AAT is expressed at normal AAT serum levels. The MM phenotype has a heterogeneous constitution and the alleles M1, M2 and M3 are distinguished by isoelectric focusing. At the DNA level many mutants of the AAT gene may exist that cannot be recognized by IEF. In this paper we report DNA sequence heterogeneity of the AAT gene region among 137 patients with COPD and 130 healthy control subjects. All 267 individuals studied were MM phenotype. Several restriction fragment length polymorphisms (RFLPs) were observed using genomic probes of the AAT gene. One allele (T2) of a Taq I RFLP located 1 kb downstream of the AAT gene was significantly more frequent in patients (15.3%) than in controls (5.4%) (P less than 0.005). The relative incidence of COPD was 3.3 times higher for subjects carrying at least one T2 allele than for the common T1T1 genotype. The T2 allele may be in linkage disequilibrium with a functionally deficient variant of AAT or some gene in close neighbourhood, e.g. the alpha 1-antichymotrypsin gene. A deletion of 1.8 kb in the alpha 1-antichymotrypsin-like gene (PIL gene) occurs at a frequency of 0.26 in patients and in control subjects as well.     

探讨MUC1基因多态性与胃癌遗传易感性的关系

目的：探讨 MUC1基因多态性与胃癌遗传易感性的关系。方法采用病例对照研究对150例胃癌患者（胃癌组）和150名健康查体正常者（对照组）的MUC1基因rs2070803单核苷酸多态性进行检测,并分析其与胃癌易感性之间的关系。结果 MUC1基因rs2070803位点3种基因型GG、GA、AA在胃癌病例组中频率分别为80.7%、16.0%和3.3%,而在对照组中分别为64.7%、32.0%和3.3%。与GG型比较,GA/AA型基因型者胃癌发生的危险性降低,OR值为0.439（0.259～0.742）。结论 MUC1基因rs2070803位点GG、GA基因型降低汉族人群的胃癌易感性。     

Association of transforming growth factor-beta1 gene polymorphisms with genetic susceptibility to nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal cancer (NPC) is multifactorial, and the genetic background may be a crucial etiologic factor. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine, it promotes tumor growth and metastasis in later stages of phase of cancer development. Variations in the DNA sequence in the TGF-beta1 gene may lead to altered TGF-beta1 production and/or activity, and so this can modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated the association of the TGF-beta1 polymorphisms and their haplotypes with the risk of NPC in a Chinese population. METHODS: We analyzed 2 single nucleotide polymorphisms (SNPs) of TGF-beta1 gene promoter -509C/T and 869T/C (Leu10Pro) at exon one in 108 patients with NPC and 120 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy. RESULTS: There were significant differences in the genotype and allele distribution of -509C/T and 869T/C (Leu10Pro) polymorphisms of the TGF-beta1 gene among cases and controls. The -509T and 869C alleles carriers were associated with a significantly increased risk of NPC as compared with the non-carriers (OR=1.64, 95% CI, 1.13-2.39, P=0.009 and OR=1.70, 95% CI, 1.17-2.46, P=0.006, respectively). Consistent with the results of the genotyping analyses, the -509T/869C haplotype was associated with a significantly increased risk of NPC as compared with the -509C/869T haplotype (OR=1.68; 95% CI, 1.14-2.48; P=0.009). CONCLUSION: TGF-beta1 -509C/T and 869T/C polymorphisms, and their haplotypes are significantly associated with the risk of NPC. Our data suggests that TGF-beta1 -509C/T and 869T/C polymorphisms could be used as genetic susceptibility markers of the NPC.     

DNA polymorphisms of the a1 -antitrypsin gene region in patients with chronic obstructive pulmonary disease

Abstract. α₁-a α₁-antitrypsin (AAT) is an important part of the defence mechanism of the lung against proteolytic attack. The Z and Null mutants of the AAT gene are associated with very low or missing serum concentrations of AAT, so that for individuals with genotypes ZZ or Null there is a very high risk of developing chronic obstructive pulmonary disease (COPD). In more than 90% of the patients suffering from COPD, however, the common MM phenotype of AAT is expressed at normal AAT serum levels. The MM phenotype has a heterogeneous constitution and the alleles Ml, M2 and M3 are distinguished by isoelectric focusing. At the DNA level many mutants of the AAT gene may exist that cannot be recognized by IEF. In this paper we report DNA sequence heterogeneity of the AAT gene region among 137 patients with COPD and 130 healthy control subjects. All 267 individuals studied were MM phenotype. Several restriction fragment length polymorphisms (RFLPs) were observed using genomic probes of the AAT gene. One allele (T2) of a Taq I RFLP located 1 kb downstream of the AAT gene was significantly more frequent in patients (15.3%) than in controls (5.4%) (P<0.005). The relative incidence of COPD was 3.3 times higher for subjects carrying at least one T2 allele than for the common T1T1 genotype. The T2 allele may be in linkage disequilibrium with a functionally deficient variant of AAT or some gene in close neighbourhood, e.g. the α₁-antichymotrypsin gene. A deletion of 1.8 kb in the α₁-antitrypsin-like gene (PIL gene) occurs at a frequency of 0.26 in patients and in control subjects as well.