Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5 UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin’s coefficient [D’]) (LC: D’ =0.03, r2: 0. 001, p= 0.8; Controls: D’ =0.29, r2: 0.08, p=0.02). Carriers of the “3 tandem repeats_insertion” haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3` UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 `UTR is more informative than TSER polymorphism in predicting increased risk.     

多巴胺D4受体基因exon Ⅲ 48bp VNTR多态性与学龄儿童气质的相关性

目的 了解多巴胺D4受体基因（DRD4）第3外显子48bp可变串联重复序列多态性（exon Ⅲ 48bp VNTR）与学龄儿童气质的相关性。方法 随机整群抽取350名8~12岁健康儿童进行问卷调查,其中一半儿童进行口腔上皮采集,其中164名儿童问卷资料完整且口腔上皮细胞中DNA浓度较高的样本纳入研究,运用PCR技术进行DRD4 exon Ⅲ 48bp VNTR分型,并分析该基因及其与环境的交互作用对气质的影响。结果 携带L-DRD4基因型儿童在活动水平、反应强度、情绪本质以及坚持性4个维度的得分均低于S-DRD4基因型儿童（P < 0.05）。母亲教养方式为拒绝/否认（OR=2.281,P < 0.05）、儿童性别（OR=2.766,P < 0.05）的主效应及儿童性别与DRD4 exon Ⅲ 48bp VNTR的交互作用对儿童活动水平有影响（OR=0.582,P < 0.05）。DRD4 exon Ⅲ 48bp VNTR主效应（OR=0.314,P < 0.01）及该基因与母亲教养方式为拒绝/否认的交互作用（OR=1.872,P < 0.01）对儿童反应强度有影响。DRD4 exon Ⅲ 48bp VNTR （OR=0.420,P < 0.05）及母亲教养方式为拒绝/否认（OR=2.236,P < 0.05）的主效应对儿童坚持性有影响。结论 DRD4 exon Ⅲ 48bp VNTR及该基因与其他因素的交互作用可能影响学龄儿童的活动水平和反应强度。     

Array comparative genomic hybridization (aCGH) reveals the largest novel deletion in PCCA found in a Saudi family with propionic acidemia

Propionic acidemia is a metabolic disorder (OMIM 606054) caused by deficiency of the propionyl-coenzyme A (CoA) carboxylase, which subsequently results in accumulation of propionic acid. Patients may initially present with poor feeding, vomiting, loss of appetite, hypotonia, and lethargy. Later, most children will show different degrees of motor, social and language delay even more serious medical problems, including heart abnormalities, seizures, coma, and possibly death. Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding α and β subunits of propionyl-coenzyme A (CoA) carboxylase, respectively. Both patients had a mild–severe form of propionic acidemia. The investigations using PCR, long-PCR, array comparative genomic hybridization (aCGH), and sequencing techniques showed a 73 kb deletion extending from intron 16 to intron 19 and an 18 bp insertion at the distal end of the deletion in PCCA gene. The deletion so far is the largest gross change reported in the literature for the PCCA gene.     

mtDNA4977bp缺失分析评价肿瘤细胞辐射敏感性的研究

目的 探讨mtDNA4977bp缺失用于肿瘤细胞辐射敏感性检测的可行性。方法 选取三种不同肿瘤细胞株:肝癌细胞(HepG₂)、食管癌细胞(EC-9706)和乳腺癌细胞(MCF-7)。采用MTT法检测肿瘤细胞经γ射线照射后的存活分数(SF);巢式PCR法检测肿瘤细胞的mtDNA4977bp缺失率。结果 MTT法:2Gy、4Gy和8Gy照射后,HepG₂和EC-9706的SF显著低于MCF-7,表明HepG₂和EC-9706细胞具有更高的辐射敏感性。PCR法:1Gy和4Gy照射后3种肿瘤细胞mtDNA4977bp缺失率差异无统计学意义,8Gy照射后HepG₂和EC-9706mtDNA4977bp缺失进一步增加,而MCF-7的缺失率下降,显著低于HepG₂与EC-9706细胞的缺失率,提示HepG₂和EC-9706细胞的辐射敏感性高于MCF-7细胞。结论 mtDNA4977bp缺失作为新的生物学指标,有希望更加客观准确地评价肿瘤细胞的辐射敏感性。     

Production and biomedical applications of virus-like particles derived from polyomaviruses

Virus-like particles (VLPs), aggregates of capsid proteins devoid of viral genetic material, show great promise in the fields of vaccine development and gene therapy. These particles spontaneously self-assemble after heterologous expression of viral structural proteins. This review will focus on the use of virus-like particles derived from polyomavirus capsid proteins. Since their first recombinant production 27 years ago these particles have been investigated for a myriad of biomedical applications. These virus-like particles are safe, easy to produce, can be loaded with a broad range of diverse cargos and can be tailored for specific delivery or epitope presentation. We will highlight the structural characteristics of polyomavirus-derived VLPs and give an overview of their applications in diagnostics, vaccine development and gene delivery.     

Molecular determination of T-cell receptor alpha and beta chain genotypes in human families

Polymorphism in genes encoding the alpha and beta chain of the human T cell receptor has been detected by Southern blot analysis. Genomic DNA samples were isolated from B lymphoblastoid cell lines derived from members of families, each family including at least one individual with a recombinant HLA haplotype. T cell receptor alpha and beta chain haplotypes could be assigned in the families on the basis of observed restriction fragment length polymorphism (RFLP). Polymorphism in the alpha chain gene was detected in BglII digests using an alpha chain probe that included the V, J, C, and 3' untranslated sequences. A probe consisting of only the constant region (C alpha) revealed no polymorphism indicating that the polymorphic fragment hybridized to V, J, or 3' untranslated sequences of the alpha chain. Polymorphism in beta chain genes was observed in BglII digested DNA samples using a probe that corresponds to the constant region (C beta). Polymorphic C beta restriction fragments of 10.0 and 9.2 kilobase segregated in six of the eight families studied. Recent structural data for the C beta region suggest that the polymorphic BglII site lies in the region 5' to the C beta 2 gene. These polymorphisms should serve as markers for alpha and beta chain complexes allowing genetic studies of these immunologically important gene families.