p53基因多态性与鼻咽癌遗传易感性的关系

目的研究广西南宁鼻咽癌患者p53基因遗传多态性与鼻咽癌发生的关系。方法采用病例-对照研究方法,以200例鼻咽癌患者、200例对照人群为研究对象。选取p53基因SNP rs117562731位点作为遗传标记,用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)和测序方法检测rs117562731位点基因型频率和等位基因频率,比较两组不同基因型与鼻咽癌易感性的关系。结果通过对rs117562731位点多态基因型检测分型发现,在鼻咽癌组和对照组CC、CT、TT基因型频率分别为80.0%、17.0%、3.0%和93.0%、5.5%、1.5%。rs117562731位点等位基因及基因型频率在鼻咽癌组与对照组间分布有显著性差异(P0.05)。结论 p53基因SNP rs117562731位点多态性与鼻咽癌之间存在显著的相关性。     

p53PIN3基因多态性与早发性乳腺癌易感性的关系

目的探讨p53PIN3基因多态性与早发性乳腺癌遗传易感性之间的关系。方法采用序列特异性引物,以PCR方法检测114例早发性乳腺癌患者和124例健康对照个体外周血DNAp53基因第3内含子的基因型。结果乳腺癌组与健康对照组间p53基因第3内含子16bp插入或缺失序列(PIN3)的A、A′等位基因频率分别为91.23%、8.77%及96.37%、3.63%,两组比较有显著差异(χ2=5.492,P<0.05);两组间AA、AA′、A′A′3种基因型频率比较,基因型分布有统计学差异(χ2=5.873,P<0.05)。乳腺癌组中根据手术病理分组,Ⅰ～Ⅱ与Ⅲ～Ⅳ期乳腺癌等位基因和基因型频率比较无显著差异(χ2=0.050,P>0.900和χ2=0.055,P>0.900);根据肿瘤大小比较等位基因和基因型频率,差异无显著性(χ2=0.020,P>0.05和χ2=0.018,P>0.05);根据淋巴结转移与否比较等位基因和基因型频率,差异也无显著性(χ2=0.102,P>0.05和χ2=0.092,P>0.05)。结论p53第3内含子基因多态性与贵州地区妇女早发性乳腺癌遗传易感性存在相关性。     

LOX-1 3′-UTR+1073多态性与冠心病的相关性

目的探讨血凝素样氧化低密度脂蛋白受体（LOX）-1基因中3′-UTR+1073位点（C/T）基因型多态性与冠心病的遗传易感性的关系。方法采用PCR和限制性片段长度多态性（RFLP）分析方法对LOX-1 3′-UTR+1073位点C/T基因型多态性进行检测,观察其在101例冠心病患者（其中61例心肌梗死患者）和54例对照中的频率分布。并与冠心病危险因素和临床情况相结合进行综合分析。结果①LOX-1 3′-UTR+1073基因CC、CT与TT基因型及C、T等位基因在冠心病组和对照组中分布频率无显著差异;在心肌梗死组和对照组中分布频率无显著差异;②在具有相同危险因素（高血压、糖尿病、吸烟）的人群中,3′-UTR+1073基因CC、CT与TT基因型在患冠心病和不患冠心病者分布频率无显著意义。结论LOX-1 3′-UTR+1073基因的基因型多态性与冠心病可能无关,不能作为冠心病的遗传易感标志。     

IL-28B基因多态性与丙型肝炎易感性的关系

目的:探讨白介素-28B(interleukin-28B,IL-28B)单核苷酸多态性位点rs8099917与中国丙型肝炎易感性的关系.方法:采用TaqMan SNP基因分型的方法检测中国天津地区263名丙型肝炎患者和244名健康人IL-28B rs8099917基因型和等位基因分布情况,并统计分析rs8099917基因型和等位基因在2组中分布的差异.结果:在263名丙型肝炎患者中,TT基因型223人(84.8%),TG基因型39人(14.8%),GG基因型1人(0.4%).T等位基因频率为92.2%.244名健康对照者中,TT基因型222人(91.0%),TG21人(8.60%),GG1人(0.40%),T等位基因频率为95.3%.丙型肝炎患者和健康人群TG/GG基因型频率差异有统计学意义(OR=1.810,95%CI:1.042-3.145;P=0.033).丙型肝炎患者G等位基因频率也高于健康人(OR=1.709,95%CI:1.010-2.893;P=0.044).结论:中国人群IL-28B rs8099917基因多态性与丙型肝炎病毒(hepatitis C virus,HCV)感染易感性相关联.G为HCV感染的风险等位基因.     

新疆哈萨克族人群结核病易感基因的病例对照研究

目的研究自然抗性相关巨噬细胞蛋白1(NRAMPl)基因3′端非编码区(3′UTR)和维生素D受体(VDR)基因FokI、TaqI位点多态性与新疆哈萨克族人群结核病易感性的关联;分析NRAMPl基因和VDR基因交互作用对新疆哈萨克族人群结核病易感性的影响。方法采用病例对照研究方法,选取新疆哈萨克族活动性肺结核病患者213例,同地区同种族健康者211例。用聚合酶链反应 限制性片断长度多态性(PCR RFLP)分析方法对NRAMP1基因3′UTR、VDR基因FokI和TaqI多态性位点基因分型,采用χ2检验分析3个位点多态性与新疆哈萨克族结核病易感性的关系,相乘模型分析NRAMPl基因和VDR基因交互作用。结果1. NRAMPl基因3′UTR位点在病例组和对照组中TGTG/TGTG、TGTG/del和TGTGdel/del基因型频率分别为64.8%、29.6%、5.6%和79.1%、19.5%、1.4%。TGTGdel等位基因组间分布差异有统计学意义(χ2=13.737,P<0.01)。2. VDR基因FokI位点在病例组和在对照组中FF、Ff和ff基因型频率分别为33.8%、45.1%、21.1%和47.9%、41.7%、10.4%。f等位基因频率组间分布差异有统计学意义(χ2=13.868,P<0.01);TaqI位点TT、Tt和tt基因型组间分布差异无统计学意义;等位基因T和t组间分布差异无统计学意义(χ2=1.267,P>0.05);D'=0.477,r2=0.01,两位点不存在连锁不平衡。3. NRAMP1基因和VDR基因存在正交互作用,ORint=1.62。结论1. TGTG/del和TGTGdel/del基因型、TGTG缺失等位基因可能是新疆哈萨克族人群结核病易感基因。2. VDR基因中FokI多态性与新疆哈萨克族结核病易感性有关联,等位基因f可能是新疆哈萨克族结核病易感基因。3. NRAMP1和VDR基因间交互作用可能增加新疆哈萨克族人群结核病的发病风险。     

甘肃人群NQO1基因多态性与急性髓系白血病易感性的关系

目的：研究醌氧化还原酶（NQO1）基因多态性和急性髓系白血病易感性的关系。方法：用1：1配对病例-对照方法,PCR-LDR方法,对78例急性髓系白血病患者（AML）和100例对照人群进行NQO1基因突变分析。结果：AML病例组NQO1基因T等位基因频率（43%）和TC/TT基因型频率（63%）均高于对照组（28%和43%）。携带TC/TT基因型的个体发生AML的相对风险度为其野生型（CC）的1.67倍（95%CI=1.212～2.727）。结论：NQO1基因多态性与AML遗传易感性相关,等位基因C对AML易感性有保护作用。     

浙江温州地区人群染色体9p21上rs1333049位点的单核苷酸多态性分布与冠心病的相关性

目的研究浙江温州地区汉族人群中染色体9p21上的rs1333049位点上的单核苷酸多态性（single nucleotide polymorphism,SNP）与冠心病的相关性。方法对冠心病组（至少1支主要冠状动脉内径狭窄≥50.00%）181例和对照组173例,采用聚合酶链反应和基因测序方法,检测染色体9p21上rs1333049位点基因多态性。结果 3种基因型均可在rs1333049位点上检测到,并且其基因型的分布亦符合Hardy-Weinberg平衡定律。冠心病组rs13330^149位点的CC、CG基因型分布及C等位基因频率均高于对照组,差异有统计学意义（均P〈0.01）。结论 rs1333049位点G/C基因的多态性与冠心病发病相关,其中的C等位基因亦可能是浙江温州地区汉族人群冠心病患者的易感性标志之一。     

MTHFR基因和β纤维蛋白原455G/A基因多态性与脑梗死的遗传易感性

目的探讨MTHFR基因和β纤维蛋白原455G/A(βFib 455G/A)基因多态性与脑梗死的遗传易感性。方法运用PCR-RFLP检测154例脑梗死患者(脑梗死组)和83例健康体检者(对照组)MTHFR和βFib 455G/A基因多态性,同时检测纤维蛋白原(Fib)和血浆同型半胱氨酸水平等生化指标。结果脑梗死组患者MTHFR基因的CC、CT、TT基因型频率分别为21.4%、48.1%和30.5%,对照组分别为57.8%、25.3%和16.9%,脑梗死组TT基因型相对危险性为对照组的2.16倍;脑梗死组βFib 455G/A基因GG、GA、AA基因型频率分别为51.3%、40.3%和8.4%,对照组分别为72.3%、21.7%和6.0%。与对照组比较,脑梗死组患者GA基因型和A等位基因频率明显增高(P<0.05);具有CT+AA基因型或TT+GA基因型个体易患脑梗死,相对危险性为2.7和2.2。结论MTHFR基因突变后T等位基因和βFib基因突变后的A等位基因可能是脑梗死发生的一个遗传易感基因,MTHFR基因中CC型可能是脑梗死的保护因子,MTHFR基因和βFib 455G/A基因突变间可能存在协同作用。     

CHRNA3基因-1923T＞C多态性与慢性阻塞性肺疾病易感性的关系

目的 探讨尼古丁胆碱能受体3 （CHRNA3）基因-1923T＞C多态性与慢性阻塞性肺疾病（COPD）遗传易感性的关系.方法 采用聚合酶链反应-限制性片段长度多态性（PCR-RELP）方法对100例COPD患者（COPD组）及年龄性别相匹配的100例健康对照人群（对照组）的CHRNA3基因-1923T＞C多态性等位基因进行检测,并分析基因型频率.结果 COPD组TT、TC和CC基因型频率分别为24％、45％和31％,对照组分别为37％、48％和15％,两组相比,P均＜0.05;COPD组C等位基因频率（53.5％）与对照组（39.0％）相比,P＜0.01.结论 CHRNA3基因-1923T＞C多态性可能与COPD遗传易感性增加有关,C等位基因可能是COPD发生的重要危险因素.     

花生四烯酸5-脂氧合酶激活蛋白基因多态性与急性冠状动脉综合征的易感性

目的探讨花生四烯酸5脂氧合酶激活蛋白(ALOX5AP)基因SG1 3S114T/A多态性与急性冠状动脉综合征(ACS)的易感性。方法选择住院的胸痛患者714例,将确诊为ACS的患者377例作为ACS组,非ACS患者337例作为对照组,采用聚合酶链反应限制性片段长度多态性方法检测ALOX5AP基因SG13S114T/A多态性,并进行logistic回归分析。结果 ACS组患者AA、AT和TT基因型频率分别为1 3.79%、50.93%和35.28%,对照组患者分别为12.76%、38.58%和48.66%,2组AT和TT基因型频率差异有统计学意义(P=0.041,0.020);ACS组男性AT基因型频率高于对照组(P=0.040),女性TT基因型频率低于对照组(P=0.013)。SG13S114T/A位点AT和TT基因型以及T等位基因是所有ACS(P=0.004、0.001和0.013)和男性ACS(P=0.014、0.005和0.020)发病的危险因素。结论 ALOX5AP基因SG1 3S114T/A多态性AT和TT基因型以及T等位基因可能与老年人,特别是老年男性ACS的易感性相关。     

Structure of the Sec23p/24p and Sec13p/31p complexes of COPII

COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi complex. This vesicular transport can be reconstituted by using three cytosolic components containing five proteins: the small GTPase Sar1p, the Sec23p/24p complex, and the Sec13p/Sec31p complex. We have used a combination of biochemistry and electron microscopy to investigate the molecular organization and structure of Sec23p/24p and Sec13p/31p complexes. The three-dimensional reconstruction of Sec23p/24p reveals that it has a bone-shaped structure, (17 nm in length), composed of two similar globular domains, one corresponding to Sec23p and the other to Sec24p. Sec13p/31p is a heterotetramer composed of two copies of Sec13p and two copies of Sec31p. It has an elongated shape, is 28-30 nm in length, and contains five consecutive globular domains linked by relatively flexible joints. Putting together the architecture of these Sec complexes with the interactions between their subunits and the appearance of the coat in COPII-coated vesicles, we present a model for COPII coat organization.     

Chromosome 17p and p53 changes in lymphoma

The clinical course of lymphoma patients in whom rearrangements or deletions of the short arm of chromosome 17 (17p) were evident by cytogenetics was rapidly progressive with a short survival. The gene for the protein designated p53 resides in 17p. We studied four lymphoma cell lines derived from human tumours, and 25 tumour samples of patients with lymphomas, for any evidence of p53 genomic changes by Southern blot technique. The four cell lines and four of the 25 tumour samples showed numerical changes of chromosome 17 or structural abnormalities of 17p (translocations or deletions). Allelic loss of the p53 gene was found in two of the four cell lines, and one of these in addition showed a rearrangement of the 3' end of the gene. Of the four tumours known to have chromosome 17 abnormality, one specimen showed allelic loss of the p53 gene. None of the remaining tumour samples showed any significant change. These studies suggest that acquisition of changes in the short arm of chromosome 17, which may be interrelated with the p53 gene, may carry a poor prognosis in patients with non-Hodgkin's lymphoma.     

Contribution of p53, p63, and p73 to the developmental diseases and cancer

Tumor suppressor TP53 gene is one of the most mutated genes in human genome. Inactivating somatic mutations and disruption of p53 protein have been described in almost all human malignancies. Its inactivation by germline mutation leads to the rare but severe familial precancerosis termed Li-Fraumeni syndrome. This syndrome is characterized by the early onset of different types of cancers including soft-tissue sarcomas, breast and brain cancers, leukemias, lung, laryngeal cancers, and adrenocortical carcinomas. The key role of p53 in tumor suppression has been confirmed in animal models as well. The p53 -knock-out and knock-in animals were born alive but were tumor prone. In the late nineties, two genes with high homology with TP53 were discovered, TP73 and TP63, respectively. Animal models showed that p73 is an important player in neurogenesis, sensory pathways and homeostatic control. The p63 is critical for the development of stratified epithelial tissues such as epidermis, breast, and prostate. Despite the structural similarities with p53, the function of these proteins in tumorigenesis is controversial. On one hand, there are evidences that both, p63 and p73-deficient animals are not tumor prone; on the other hand, there is evidence that such animals develop tumors later during their life. Unlike in TP53 gene, mutations in TP63 and TP73 genes are rare, however, germline mutations in TP63 are linked to the human developmental diseases. In this minireview, we describe the contribution of the p53, p63, and p73 to human pathology with emphasis on their different roles in development and tumorigenesis.     

Immunohistochemical Expression of p16, p53, and p63 in Colorectal Adenomas and Adenocarcinomas

Purpose The aim of this study was to investigate the immunohistochemical expression of p16, p53, and p63 proteins according to some pathologic parameters related to colorectal adenomas and adenocarcinomas such as grade of dysplasia and histologic type. Methods Immunohistochemistry with the antibodies p16, p53, and p63 was performed in tubular, tubular-villous, and villous adenomas (n = 30) and in well, moderately, and poorly differentiated adenocarcinomas (n = 30). The p63-positive cases were submitted to double immunolabeling with the cytokeratin 5 (CK5). Results The p16 and p53 labelings were observed in some adenomas and adenocarcinomas but without any association with p63 expression, histologic type, or grade of differentiation of the neoplasm. P63 expression was found mainly in the villous adenomas and in the poorly differentiated adenocarcinomas. The poorly differentiated adenocarcinomas also exhibited coexpression of CK5 and p63. Conclusions Despite both p16 and p53 having been detected in colorectal neoplasms, they were not related to the different histologic variables nor to the expression of p63. However, p63 expression was closely associated with villous adenomas and poorly differentiated adenocarcinomas. Thus, p63 may represent a marker of poor differentiation in colorectal neoplasms. The coexpression of p63 and CK5 observed in this study could be related to divergent differentiation during the development of colorectal cancer, although further studies are warranted to refine the understanding of this process.     

Immunodominant epitopes of HIV-1 p17 and p24.

Immunodominant antibody-binding sites were mapped using overlapping synthetic peptides of the structural proteins p17 and p24 of human immunodeficiency virus type 1 (HIV-1). Using sera from HIV-1-infected individuals at a variety of disease states, three major epitopes were identified within p17 and one within p24. Antibodies which recognized these epitopes were present in all risk groups throughout all stages of HIV infection, regardless of the presence of high levels of serum p24 antigen.     

p73和p51基因在结直肠癌中的表达和意义

背景：p53基因是一种肿瘤抑制基因，其家族成员p73和p51在结构上与p53具有高度同源性，影响细胞转录和凋亡的功能与p53相似。目的：研究p73和p51基因在结直肠癌中的表达及其与细胞凋亡和肿瘤临床病理特征的关系，探讨两者在结直肠癌发生、发展中的可能作用。方法：以逆转录聚合酶链反应（RT—PCR）检测60例结直肠癌组织和相应癌旁组织中p73、p51mRNA表达，以原位末端标记（TUNEL）法检测细胞凋亡。结果：结直肠癌组织p73、p51AmRNA表达阳性率显著高于相应癌旁组织（p73：71．7％对5．0％，P〈0．01：p51A：46．7％对11．7％，P〈0．01）：p51B mRNA在结直肠癌组织与相应癌旁组织中的相对表达量无明显差异（0．7318±0．3628对0．6836±0．3516，P〉0．05）。p73、p51A mRNA表达阳性者肿瘤细胞凋亡指数分别显著低于p73、p51A mRNA表达阴性者（p73：3．2％±2．5％对5．5％±2．8％．P=0．003；p51A：2．6％±2．3％对4．9％±2．7％，P=0．001）。p73mRNA表达与结直肠癌的分化程度、TNM分期和淋巴结转移相关（P〈0．05），p51A mRNA表达仅与淋巴结转移相关（P〈0．05）。结论：结直肠癌中p73、p51A基因表达上调，两者可能通过抑制肿瘤细胞凋亡而参与了结直肠癌的发生、发展。p73过表达可能与结直肠癌预后不良有关。