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Frequency of GSTT1*0 genotype as a non-conjugator phenotype in a group of healthy Iranian people

机译:一群健康的伊朗人中GSTT1 * 0基因型作为非共轭表型的频率

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Glutathione S-transferases (GSTs) are dimeric mainly cytosolic enzymes involved in detoxification of many exogenous and endogenous disease-causing electrophilic substrates. GSTs also have critical role in phase II biotransformation of a number of drugs, xenobiotics and industrial chemicals and protect cellular macromolecules. The evidences supported that human GSTT1 contributes in the deactivation of reactive oxygen species which more likely to be effective in inflammatory diseases, ageing and some non-cancer diseases also different types of cancers. The GSTT1 is genetically deleted in a high percentage of the different ethnic groups. Although this gene is highly conserved during evolution, it is indeed surprising that the GSTT1 deleted gene could be found in high incidence of human population. Conjugator and non-conjugator phenotypes are coincident with this deletion (GSTT1*1 and GSTT1*0 genotype).The consequences of this deletion could be involved in some diseases outcome, toxicology and drug resistances. In this study the Real-time PCR assay and a set of hybridization probes was used as a one-step and accurate method to estimate the frequency of GSTT1*0 genotype as a non-functional phenotype in 90 healthy individuals from the province of Isfahan in Iran. GSTT1 genotypes were identified in DNA samples using fluorogenic Real-Time PCR (LightCycler) followed by online melting curve analysis. The incidence of GSTT1*1(wild type) and GSTT1*0(Null type) were 74.5% and 25.5% respectively. No differences in genotypes frequencies were perceived in samples stratified by age and gender P> 0.05. The results were compared with other ethnic groups to get more insight into the frequency differences of defected carcinogens metabolizer gene due to deletion polymorphism of GSTT1. It has been indicated the incidence of GSTT1*0 in this group of Iran showed significant differences with East Asian and some European and American countries P< 0.05.The prevalence of GSTT1 null genotype in the study group from Isfahan province of Iran was slightly higher in comparison with other Iranian ethnic group (Iranian Georgian 15.7%), but this difference was not significant (χ2=1.66, P=0.197). Further experimental investigations are needed to inquiry the clinical implications of GSTT1 genetic polymorphism with consider to significant variability among different ethnicities.
机译:谷胱甘肽S-转移酶(GST)是二聚体,主要是胞质酶,参与许多外源性和内源性致病性亲电子底物的解毒。 GST在许多药物,异生物素和工业化学品的II期生物转化中也起着关键作用,并保护细胞大分子。证据支持人GSTT1导致活性氧的失活,而活性氧更可能有效用于治疗炎症性疾病,衰老和某些非癌症疾病以及不同类型的癌症。 GSTT1在很多种族中被遗传删除。尽管该基因在进化过程中是高度保守的,但确实令人惊讶的是,在人类高发人群中发现了GSTT1缺失的基因。缀合和非缀合的表型与该缺失相符(GSTT1 * 1和GSTT1 * 0基因型)。这种缺失的后果可能与某些疾病的预后,毒理学和耐药性有关。在这项研究中,实时荧光定量PCR检测和一套杂交探针被用作一步一步且准确的方法来估计来自伊斯法罕省的90名健康个体中GSTT1 * 0基因型作为非功能性表型的频率。伊朗。使用荧光实时荧光定量PCR(LightCycler)在DNA样品中鉴定GSTT1基因型,然后进行在线熔解曲线分析。 GSTT1 * 1(野生型)和GSTT1 * 0(空型)的发生率分别为74.5 %和25.5 %。在按年龄和性别分层的样本中,基因型频率没有差异(P> 0.05)。将结果与其他种族进行比较,以更深入地了解由于GSTT1缺失多态性导致的致癌物质代谢缺陷基因的频率差异。研究表明,该组伊朗人群中GSTT1 * 0的发生率与东亚和一些欧美国家存在显着差异,P <0.05。伊朗伊斯法罕省研究组中GSTT1无效基因型的患病率略高。与其他伊朗族裔相比(伊朗格鲁吉亚族人占15.7%),但这种差异并不显着(χ2= 1.66,P = 0.197)。需要进一步的实验研究来询问GSTT1遗传多态性的临床意义,同时考虑到不同种族之间的显着差异。

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