Ⅰ型糖尿病患者的HLA-DR基因单体型分析

目的：揭示中国人ＩＤＤＭ的遗传分子基础。方法：应用分子生物学研究方法,对ＨＬＡ－ＤＲＢ进行序列特异性引物的ＰＣＲ扩增,鉴定了８１例ＩＤＤＭ患者和８４例正常对照汉族人群的ＤＲＢ基因多态性。结果：ＩＤＤＭ患者中ＤＲＢ１＊０３,ＤＲＢ１＊９等位基因频率明显高于对照组,其频率分别为８．６４％Ｖ．Ｓ３．０％和２８．４％Ｖ．Ｓ１６．１％（Ｐ〈０．０５）;ＩＤＤＭ患者中ＤＲＢ１－ＤＲＢ３／ＤＲＢ１－ＤＲＢ４基因     

应用PCR—直接测序法测定结核分支杆菌rpsL基因突变的研究

目的：了解我国结核分支杆菌耐链霉素（Ｓｔｒｅｐｔｏｍｙｃｉｎ,ＳＭ）分离株ｒｐｓＬ基因突变情况,建立快速检测结核分支杆菌耐药基因型的分子药敏试验方法。方法：通过聚合酶链反应（ＰｏｌｙｍｅｒａｓｅＣｈａｉｎＲｅａｃｔｉｏｎ,ＰＣＲ）－单链构象多态性（Ｓｉｎｇｌｅ－ｓｔｒａｎｄｅｄＣｏｎｆｏｒｍａｔｉｏｎＰｏｌｙｍｏｒｐｈｉｓｍ,ＳＳＣＰ）、ＰＣＲ－限制性片段长度多态性（ＲｅｓｔｒｉｃｔｉｏｎＦｒａｇｍｅｎｔＬｅｎｇｔｈＰｏｌｙｍｏｒｐｈｉｓｍ,ＲＦＬＰ）和ＰＣＲ－直接测序法（ＤｉｒｅｃｔＳｅｑｕｅｎｃｉｎｇ,ＤＳ）分析３８株结核分支杆菌耐ＳＭ分离株的ｒｐｓＬ基因。结果３８株耐ＳＭ分离株中,２５株ＳＳＣＰ异常、不被ＭｂｏⅡ消化、ＤＳ分析４３位密码子ＡＡＧ→ＡＧＧ突变;１株ＳＳＣＰ异常、可被ＭｂｏⅡ消化、ＤＳ分析３３位密码子ＧＴＡ→ＡＴＡ突变;１２株ＳＳＣＰ正常、可被ＭｂｏⅡ消化、ＤＳ分析未见异常;未发现８８位密码子突变。结论：大多数结核分支杆菌耐ＳＭ是由于其ｒｐｓＬ基因４３位密码子突变所致,采用ＰＣＲ－ＳＳＣＰ、ＰＣＲ－ＲＦＬＰ和ＰＣＲ－ＤＳ方法可快速测定部分结核分支杆菌ＳＭ耐药基因型。     

畲族红细胞ACP1、6－PGD、ADA和AK1的遗传多态性

用淀粉凝胶电泳结合特异酶染色方法研究１２６名畲族人红细胞酸性磷酸酶（ＡＣＰ１）、６－磷酸葡萄糖酸脱氢酶（６－ＰＧＤ）、腺苷脱氨酶（ＡＤＡ）、腺苷酸激酶（ＡＫＩ）的遗传多态性。ＡＣＰ１、６－ＰＧＤ、ＡＤＡ、ＡＫ１各位点的各等位基因频率分别为：ＡＣＰＩＡ０．１８２５、ＡＣＰ１Ｂ０．８１７５、６－ＰＧＤＡ０．９６８３、６－ＰＧＤＢ０．０２７８、ＡＤＡ１０．９８８１、ＡＤＡ２０．０１１９、ＡＫ１１１．０００。畲族ＡＣＰ１、６－ＰＧＤ和ＡＤＡ等位点为多态，ＡＫ１位点为单态。发现１个６－ＰＧＤＲ变异等位基因。     

武汉地区健康汉族人小肠脂肪酸结合蛋白基因的多态性研究

为了解武汉地区健康汉族人小肠脂肪酸结合蛋白基因（ＦＡＢＰα） 多态性,应用聚合酶链反应（ＰＣＲ） 技术检测１２０ 例对象的ＦＡＢＰαＨｈａＩ位点的限制性片段长度多态性（ＲＦＬＰｓ） 。结果显示,武汉地区健康汉族人存在ＦＡＢＰα多态性。     

酒精性肝硬化与MHC—Ⅱ类基因多态性的相关研究

目的 探讨酒精性肝硬化的致病易感性与人类免疫遗传基因ＭＨＣ－ＤＲ的关系。方法 应用聚合酶链式反应（ＰＣＲ）和序列特异性引物（ＳＳＰ）检测技术。对酒精性肝硬化患者２８例及３０例无血缘关系的健康人ＭＨＣ－ＤＲ基因多态性进行了对比研究。结果表明：人类ＭＨＣ－ＤＲＢ１＊０１３０１等位基因（ＲＲ＝１３．７５，Ｐ〈０．０１）与酒精性肝硬化致病易感性相关，而ＭＨＣ－ＤＲ其它各等位基因未见关联。结论 提示了人类Ｍ     

Graves病T,B细胞功能异常及甲巯咪唑体外调节作用的研究

目的：探讨Ｇｒａｖｅｓ病（ＧＤ）患者Ｔ、Ｂ细胞异常及甲巯咪唑体外对它们的影响。方法：将２５例ＧＤ病人 外周血单个核细胞（ＰＢＭＣ）在不同浓度的甲巯咪唑条件下进行体外细胞培养６天后,同时检测Ｔ细胞亚群及ｓＩＬ－ ２Ｒ和ＩｇＧ的含量。结果：ＧＤ病人ＰＢＭＣ中的ＣＤ_８~＋Ｔ细胞亚群百分率明显低于对照组,ＣＤ~＋_４／ＣＤ_８~＋比值显著升高 （ｐ＜０．０１）。 ｓＩＬ－２Ｒ及ＩｇＧ水平较对照组显著升高（ｐ＜０．０１）;Ｘ１０~（－５）ｍｏｌ／Ｌ的甲巯咪唑可明显升高ＧＤ患者ＰＢ－ ＭＣ培养后ＣＤ_８~＋ Ｔ细胞的百分率（Ｐ＜０．０１）,降低ＣＤ_４~８ＣＤ_８~＋比值及ｓＩＬ－２Ｒ和ＩｇＧ水平（Ｐ＜０．０１）。提示：ＧＤ病 人Ｔ细胞亚群对免疫应答发生调节失衡,甲巯咪唑具有调节ＧＤ患者Ｔ、Ｂ细胞功能异常的作用。     

（2R,3R）—酒石酸二甲酯制备的改进

（２Ｒ，３Ｒ）┐酒石酸二甲酯制备的改进ＩＭＰＲＯＶＥＤＰＲＥＰＡＲＡＴＩＯＮＯＦ（２Ｒ，３Ｒ）┐ＴＡＲＴＡＲＩＣＡＣＩＤＤＩＭＥＴＨＹＬＥＳＴＥＲ南柱石胥波（湖北制药厂医药研究所，襄樊４４１０２３）ＮＡＮＺｈｕ－Ｓｈｉ，ＸＵＢｏ（Ｉｎｓｔｉｔｕｔｅｏ...     

No functional β_3-adrenergic receptors expressed in rat skeletal muscle cells

目的：研究原代培养的大鼠骨骼肌细胞中是否存在功能性β３肾上腺素受体（β３ＡＲ）．方法：利用柱层析方法测定异丙肾上腺素（Ｉｓｏ），β３ＡＲ激动剂ＣＧＰ１２１７７Ａ和β３ＡＲ拮抗剂ＳＲ５９２３０Ａ对培养骨骼肌细胞环磷腺苷（ｃＡＭＰ）生成作用．结果：Ｉｓｏ剂量依赖性刺激骨骼肌细胞ｃＡＭＰ的生成，ＥＣ５０为１５１ｎｍｏｌ·Ｌ－１．普萘洛尔０．１μｍｏｌ·Ｌ－１抑制Ｉｓｏ刺激的ｃＡＭＰ的生成，ＫＢ值为３４７ｎｍｏｌ·Ｌ－１．ＣＧＰ１２１７７Ａ无刺激ｃＡＭＰ生成作用，但可抑制Ｉｓｏ的作用．ＳＲ５９２３０Ａ１０ｎｍｏｌ·Ｌ－１不能抑制Ｉｓｏ刺激ｃＡＭＰ的产生．结论：大鼠骨骼肌细胞中不存在功能性β３ＡＲ或至少不与腺苷酸环化酶耦联     

21-1 在金黄色葡萄球菌中编码新的青霉素结合蛋白PBP2B的基因pbpF的克隆及性质分析

青霉素结合蛋白（ＰＢＰ）为膜结合性酶,催化细菌粘肽合成中的羧肽酶和转肽酶反应。在甲氧西林敏感性金黄色葡萄球菌（ＭＳＳＡ）中已证实存在４种ＰＢＰ,即ＰＢＰ１（８５ｋＤａ）、ＰＢＰ２（８１ｋＤａ）、ＰＢＰ３（７５ｋＤａ）和ＰＢＰ４（４５ｋＤａ）,此外在甲氧西林耐药性金黄色葡萄球菌（ＭＲＳＡ）中还有ＰＢＰ２＇（Ａ）。金黄色葡萄球菌中的ＰＢＰ为β－内酞胺类抗生素的作用靶位,由于β－内酰胺类抗生素与这些ＰＢＰ结合,而抑制金黄色葡萄球菌细胞壁的生物合成。在ＭＲＳＡ中,ＰＢＰ２＇（Ａ）与β－内酰胺类抗生素的亲…     

通关藤中新C_（21）－甾体甙的化学结构研究

从通关藤（Ｍａｒｓｄｅｎｉａｔｅｎａｃｉｓｓｉｍａ（Ｒｏｘｂ．）ＷｉｇｈｔｅｔＡｒｎ）中分得多个Ｃ_（２１），甾体甙类化合物。通过ＦＡＢＭＳ、￣１ＨＮＭＲ、￣（１３）ＣＮＭＲ、￣１Ｈ－￣１ＨＣＯＳＹ、ＬＳＰＤ、ＴＯＣＳＹ、ＨＭＱＣ、ＨＭＢＣ等光谱分析，确定了其中３个新化合物的化学结构。     

The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson's disease, levodopa treatment response, and complications

INTRODUCTION: Differences in catechol-O-methyltransferase (COMT) activity and genotype may determine individual variations in the therapeutic response to levodopa or Parkinson's disease (PD) susceptibility. The role of functional COMT haplotypes in PD susceptibility and treatment response has not been examined. OBJECTIVES: In this case-control study, we investigated the association of the most common COMT gene haplotypes (formed by single nucleotide polymorphisms (SNPs): rs6269:A>G; rs4633C>T; rs4818:C>G; and rs4680:A>G) with PD risk and the association of the COMT haplotypes with the dose and complications of levodopa therapy in PD patients. METHODS: A total of 679 study participants (322 PD and 357 controls) were included. Each participant was genotyped for four SNPs in the COMT gene, located in a common haploblock, that has been shown to influence COMT enzymatic activity. The influence of COMT haplotypes on the dose of levodopa administered during fifth year of treatment, and occurrence of motor complications were examined in PD patients. The EH program (Jurg Ott, Rockefeller University, New York, USA) was used to estimate haplotype frequencies. RESULTS: The estimated frequencies of low (A_C_C_G) and medium (A_T_C_A) activity haplotypes tended to be slightly lower among PD patients when compared with controls (P=0.09, G_C_G_G-high activity haplotype as reference). The frequency of G_C_G_G (high activity) haplotype carriers was higher in late onset PD patients (P=0.04) compared with controls. The mean levodopa dose increased with the activity of the functional haplotypes (low相似文献   

No significant associations between two dopamine receptor polymorphisms and normal temperament

A replicated association has been reported between the normal personality trait of novelty seeking on the Tridimensional Personality Questionnaire (TPQ) and an exon III polymorphism in the dopamine D4 receptor gene (D4DR). Genotyping of a polymorphism in exon I of the same gene was carried out in 124 normal volunteers, and no association was found with any TPQ trait. In the same volunteers a dopamine D3 receptor gene (D3DR) point mutation in exon 1 was genotyped. Again, no overall association between any TPQ trait and alleles or genotype was found. There was a weak association between D3DR exon I genotype and harm avoidance in males only. © 1998 John Wiley & Sons, Ltd.     

Association between three functional polymorphisms of the dopamine D2 receptor gene and polydipsia in schizophrenia

The underlying pathophysiology of polydipsia in schizophrenia is poorly understood. However, several studies suggest there may be a genetic predisposition to polydipsia, including our previous study demonstrating familial concordance of polydipsia among first-degree relatives with schizophrenia. Antipsychotic medications may contribute to the development of polydipsia and studies show that dopamine D2 receptors are involved in drinking behaviour pathophysiology. Our hypothesis is that polymorphisms in the dopamine D2 receptor gene (DRD2) may confer susceptibility to polydipsia in schizophrenia. We tested for an association between polydipsia in schizophrenia and three functional polymorphisms of DRD2. The three polymorphisms, -141C Ins/Del, Ser311Cys, and TaqIA, were genotyped in patients with polydipsia (n = 64) and in those without polydipsia (n = 91). Of the three polymorphisms, TaqIA was significantly associated with polydipsia [genotype: chi2 = 6.59, df = 2, p = 0.037; allele: chi2 = 6.52, df = 1, p = 0.011, OR 1.81, 95% CI 1.15-2.86]. Haplotype analysis of the three markers found increased significance of the association (global, p = 0.00091). Although based on a relatively small portion of the sample, individual comparison of the common haplotypes showed that haplotype Ins-Cys-A1 was significantly less frequent in patients with polydipsia (p = 0.00082). The present data suggests polymorphisms in DRD2 may confer susceptibility to polydipsia in schizophrenia. To confirm our findings, further studies are warranted on larger samples using more extensive biological measures for diagnosing the polydipsia phenotype.     

人类MnSOD基因多态性与帕金森氏病的遗传易感性的相关研究

目的 :研究人类锰超氧化物歧化酶 (Mn SOD)基因的单核苷酸多态性 (SNP)与帕金森氏病 (PD)的遗传易感性的关系 ,为寻找 PD的易感基因或抗病基因提供线索。方法 :应用聚合酶链反应 -限制性片段长度多态性技术 (PCR- RFL P)对 14 0例日本 PD患者和 2 0 0例正常健康对照者进行 Mn SOD线粒体靶序列的 1183位点 T/ CSNP频率检测 ,此一基因替换导致Mn SOD第 9位的缬氨酸 (GTT)被丙氨酸 (GCT )取代。结果 :与对照组相比 ,PD患者组的 C等位基因频率明显升高(P<0 .0 5 )。结论 :PD患者的 Mn SOD线粒体靶序列的编码丙氨酸的等位基因 C与该病的的遗传易感性相关     

人类白细胞抗原—DRB基因多态性与IgE介导综合征相关性研究

目的探讨IgE介导综合征与HLA-DRB基因多态性的相关性,研究HLA-DRB等位基因与血清总IgE(TIgE)间的关系.方法用引物序列特异性聚合酶链反应(PCR-SSCP)扩增HLA-DRB等位基因,用酶联免疫吸附实验(ELISA)检测血清TIgE,用皮肤过敏实验进行皮肤过敏原检测.结果HLA-DRB等位基因在男女频率分布无显著性差异(P＞0.05);DR3基因频率患者组为13.41%,对照组为3.75%(P＜0.01,RR4.52).而DR6基因频率在患者组为0,对照组为8.75%(P＜0.01).DR1等位基因与TIgE之间有显著性差异(P＜0.05),且与低浓度有关.28例皮肤过敏原检测结果显示尘螨的检出率最高.结论推测DR3基因位点是天津地区汉族IgE介导综合征的易感基因,DR6基因位点是天津地区汉族IgE介导综合征的抗性基因.HLA-DR1基因与血清TIgE有关.尘螨可能是诱发和加重该病的变应原.     

Naturalistic pharmacogenetic study of treatment resistance to typical neuroleptics in European-Brazilian schizophrenics

OBJECTIVES: This study aimed to explore the influence of variation in DRD2, DRD3, CYP2D6, CYP3A4, and CYP3A5 genes on treatment resistance to typical neuroleptics in a Brazilian sample of patients with schizophrenia. METHODS: One polymorphism at DRD2 gene, five at DRD3, 24 at CYP2D6, nine at CYP3A4 gene, and one at CYP3A5 gene were genotyped in a sample of 186 patients with schizophrenia. RESULTS: From the nine studied CYP3A4 single nucleotide polymorphisms, only the -392A>G was polymorphic, and significant associations were observed between this single nucleotide polymorphism and efficacy of neuroleptic treatment. Homozygous individuals for the -392A variant [P=0.014, odds ratio (OR)=3.32] were more frequent in the treatment-resistant group, compared with carriers of one copy of the -392G variant. The CYP3A5 low expressor genotype (CYP3A5*3/CYP3A5*3) was found to be associated with refractoriness to neuroleptic treatment (P=0.003, OR=3.16). Among the haplotypes observed in DRD3 gene, the T/A/G/A/C haplotype showed an association with refractoriness to neuroleptics (chi=5.342, P=0.021, OR=1.75). This association showed that carriers of one copy of this haplotype presented intermediate values between noncarriers and homozygous individuals for the haplotype. No association was observed with polymorphisms in DRD2 and CYP2D6 genes. Multiple logistic regression analyses showed that the number of copies of DRD3 T/A/G/A/C haplotype and CYP3A5 low expressor genotype were predictors of refractoriness to neuroleptic after controlling for selected risk factors. CYP3A5*3 individuals carrying at least one copy of the T/A/G/A/C haplotype showed a higher risk to be refractory to neuroleptics than CYP3A5*3 homozygotes+non-T/A/G/A/C carriers (chi=5.533, P=0.019, OR=2.32, 95% confidence interval=1.08-5.02). No significant associations were observed with DRD2 and CYP2D6 polymorphisms. CONCLUSION: Our results suggest a role for CYP3A5 and DRD3 gene variants on refractoriness to neuroleptic treatment in Brazilians with schizophrenia.     

葡萄糖脑苷脂酶基因多态性与帕金森病的相关性

目的 研究贵州人群帕金森病(PD)患者的葡萄糖脑苷脂酶(GBA)基因N370S、V394L和IA44P突变位点多态性,探讨GBA基因突变与PD的相关性.方法 选取50例PD患者和50例正常对照组的基因组DNA,通过PCR扩增GBA基因的外显子8-11 DNA片段,再以纯化的PCR产物作模板,通过PCR分别扩增GBA基因外显子9和外显子10 DNA片段,纯化后测序.结果 PD患者和正常对照组的GBA基因外显子9和外显子10核苷酸序列完全一致,未发现突变点.结论 在中国贵州人群中,GBA基因N370S、V394L和LA44P突变位点无多态性,提示GBA基因N370S、V394L和L444P突变与中国贵州人群的PD不具有相关性.     

钙黏蛋白家族成员 3及 11号染色体开放阅读框 30基因多态性与支气管哮喘病儿易感性及糖皮质激素疗效的研究

目的探讨钙黏蛋白家族成员 3(CDHR3)及 11号染色体开放阅读框 30(C11orf30,EMSY)基因多态性与支气管哮喘病儿易感性及糖皮质激素疗效。方法前瞻性选取 2020年 5月至 2021年 10月于泰州市第二人民医院就诊的支气管哮喘病儿 132例作为易感组。均接受糖皮质激素吸入治疗,并根据疗效分为疗效良好组和疗效不良组。选取同期体检的 48例儿童作为对照组,采用倾向性匹配方法对易感组和对照组性别、年龄等基线资料进行匹配;采用 PCR检测 CDHR3及 EMSY基因的单核苷酸多态性,计算其基因型频率和等位基因频率,基因位点的多态性与儿童支气管哮喘易感风险间的关系采用多因素 logistic回归分析。对比疗效良好组和疗效不良组不同基因型分布。结果易感组和对照组经倾向性评分匹配后有 36组配对成功(每组 36例),匹配后基线资料对比差异无统计学意义( P>0.05)。匹配后易感组和对照组 CDHR3基因 rs6967330位点、 EMSY基因 rs12278256位点基因型频率及 A等位基因频率比较差异有统计学意义( P<0.05)。多因素 logistic回归分析显示: EMSY基因 rs12278256位点 AA基因型［ OR=9.91,95%CI:(1.02,96.65)］、 CDHR3基因 rs6967330位点 AA基因型［ OR=10.09,95%CI:(1.08,94.02)］是支气管哮喘易感的危险因素(均 P<0.05)。治疗 12周后, 24例( 66.67%)为疗效良好组,其余 12例( 33.33%)归为疗效不佳组,两组 CDHR3基因 rs6967330位点基因型分布对比差异无统计学意义( P>0.05);两组 EMSY基因 rs12278256位点基因型分布对比差异有统计学意义( P<0.05)其中疗效良好组 AA基因型分布频率［ 37.50%(9/24)］明显高于疗效不良组［ 0(0/12)］(P<0.05)。结论 CDHR3基因 rs3847076位,点以及 EMSY基因 rs12278256位点与儿童支气管哮喘易感有关, EMSY基因 rs12278256位点与糖皮质激素治疗疗效相关。     

对氧磷酯酶基因多态性与糖尿病视网膜病变的关系(附236例分析)

目的 探讨对氧磷酯酶2(PON2)基因A148G多态性与糖尿病视网膜病变的关系。方法 (1)用聚合酶链反应—限制性片段长度多态性(PCR—RFLP)分析法探查PON2基因A148G多态性在正常对照组、单纯2型糖尿病组、糖尿病视网膜病变组中的基因分布频率；(2)放免法检测血清免疫反应性胰岛素(IRI)、C肽(C—P)水平。结果 (1)糖尿病视网膜病变组的GG基因型和G等位基因频率明显高于单纯2型糖尿病组(X^2＝3．98 P＜0.05，X^2＝4．49 P＜0.05)和正常对照组(X^2＝8．44 P＜0.01，X^2＝8．66 P＜0.01)；(2)方差分析结果显示基因型为GG的糖尿病患者空腹血糖浓度明显高于基因型为GA和AA的糖尿病患者(F＝3．94 P＜0.05，F＝5．17 P＜0.05)，而正常对照组各基因型间空腹血糖浓度无显著性差异(P＞0.05)；(3)非参数检验表明PON2基因多态性与糖尿病视网膜病变的发生有关(Z＝0．574 P＜0.05)，多因素分析结果表明PON2基因型(相对危险度为3．5471 P＜0．001，模型总判对率90．31％)和空腹血糖浓度(相对危险度为4．0143 P＜0．001，模型总判对率89．74％)与糖尿病视网膜病变独立相关。结论 PON2基因多态性与糖尿病视网膜病变有关，糖尿病视网膜病变的易感性在一定程度上与较高的空腹血糖浓度有关。