基因多态性蕴藏着大量遗传信息,分型技术是研究多态性的主要研究手段。本文建立了一个基于连接酶检测反应的基因多态性并行检测系统,该系统应用连接酶检测反应与基因芯片技术。对AGT M 235T 3种基因型和ACE I/D 3种基因型分型,同直接测...基因多态性蕴藏着大量遗传信息,分型技术是研究多态性的主要研究手段。本文建立了一个基于连接酶检测反应的基因多态性并行检测系统,该系统应用连接酶检测反应与基因芯片技术。对AGT M 235T 3种基因型和ACE I/D 3种基因型分型,同直接测序分型结果一致。将该系统应用于168份临床样本,经过统计学分析,用卡方检验发现高血压组和正常组AGT M 235T多态性存在显著差异(2χ=6.191,P<0.05),但ACE I/D多态性没有显著差异(χ2=5.241,P>0.05)。展开更多
Genetic polymorphism has a vital role in the pathogenesis and development of myocardial infarction(MI).Single nucleotide polymorphism at any one of the amino acid sequences can result in a diseased state.A single gene...Genetic polymorphism has a vital role in the pathogenesis and development of myocardial infarction(MI).Single nucleotide polymorphism at any one of the amino acid sequences can result in a diseased state.A single gene can exhibit genetic polymorphism at more than one position giving rise to different variants.Genetic polymorphism of angiotensinogen(AGT)M235T,AGT T174M,and angiotensin-1-converting enzyme(ACE)I/D,endothelial nitric oxide synthase(eNOS),and methylenetetrahydrofolate reductase(MTHFR)can be a risk factor for MI.However,it is important to study the prevalence of genetic polymorphisms of these genes among different populations.MI is influenced by genetic polymorphism of various genes,including AGT,ACE,eNOS,MTHFR,etc.However,the association of genetic polymorphism of these genes varies among different populations,but different ethnic groups could show contradictory results.These genes have shown a positive association with risks of MI in some populations,whereas the results have not been consistent with every ethnic group.In this article,we have summarized the genetic variations in the aforementioned genes and their association with MI.展开更多
目的：探讨DNA损伤修复酶基因XRCC1Arg194Trp多态性和AGT基因第三外显子Leu84Phe多态性与食管癌易感性的关系。方法：采用病例-对照研究方法分析四川北部地区食管癌病例（n=155）和年龄、性别分布无差异的对照组（n=127）XRCC1基因Arg19...目的：探讨DNA损伤修复酶基因XRCC1Arg194Trp多态性和AGT基因第三外显子Leu84Phe多态性与食管癌易感性的关系。方法：采用病例-对照研究方法分析四川北部地区食管癌病例（n=155）和年龄、性别分布无差异的对照组（n=127）XRCC1基因Arg194Trp多态性和AGT基因第三外显子Leu84Phe多态性,两个基因多态的交互作用和基因多态与吸烟、饮酒之间的交互作用对食管癌易感性的影响。结果：XRCC1基因194位点各基因型在两组间的分布无统计学差异（χ~2=0.614;P=0.736）。AGT基因第三外显子第84位密码子各基因型在两组间的分布无统计学差异（χ~2=1.826;P=0.177）,吸烟、饮酒与AGT基因第三外显子第84位密码子突变基因型TT存在正交互作用,交互作用指数（the synergy index S,S）分别为7.375、17.67。结论：四川北部地区XRCC1基因194位点基因多态性与AGT基因第三外显子Leu84Phe多态性可能与食管癌的易感性无关,但AGT基因第三外显子Leu84Phe多态性可能与吸烟、饮酒与食管癌的易感性之间存在协同作用。展开更多
The tumor selectivity of alkylating agents that produce guanine O6-chloroethyl (laromustine and carmustine) and O6-methyl (temozolomide) lesions depends upon O6-methylguanine-DNA methyltransferase (MGMT) activity bein...The tumor selectivity of alkylating agents that produce guanine O6-chloroethyl (laromustine and carmustine) and O6-methyl (temozolomide) lesions depends upon O6-methylguanine-DNA methyltransferase (MGMT) activity being lower in tumor than in host tissue. Despite the established role of MGMT as a tumor resistance factor, consensus on how to assess MGMT expression in clinical samples is unsettled. The aim of this study is to examine the relationship between the values derived from distinctive MGMT measurements in 13, 12, 6 and 2 pairs of human tumors and matched normal adjacent tissue from the colon, kidney, lung and liver, respectively, and in human cell lines. The MGMT measurements included 1) alkyl-transfer assays using [benzene-3H]O6-benzylguanine as a substrate to assess functional MGMT activity, 2) methylation-specific PCR (MSP) to probe MGMT gene promoter CpG methylations as a measure of gene silencing, and 3) western immunoblots to analyze the MGMT protein. In human cell lines, a strict negative correlation existed between MGMT activity and the extent of promoter methylation. In tissue specimens, by contrast, the correlation between these two variables was low. Moreover, alkyl-transfer assays identified 3 pairs of tumors and normal tissue with tumor-selective reduction in MGMT activity in the absence of promoter methylation. Cell line MGMT migrated as a single band in western analyses, whereas tissue MGMT was heterogeneous around its molecular size and at much higher molecular masses, indicative of multi-layered post-translational modifications. Malignancy is occasionally associated with a mobility shift in MGMT. Contrary to the prevalent expectation that MGMT expression is governed at the level of gene silencing, these data suggest that other mechanisms that can lead to tumorselective reduction in MGMT activity exist in human tissue.展开更多
文摘基因多态性蕴藏着大量遗传信息,分型技术是研究多态性的主要研究手段。本文建立了一个基于连接酶检测反应的基因多态性并行检测系统,该系统应用连接酶检测反应与基因芯片技术。对AGT M 235T 3种基因型和ACE I/D 3种基因型分型,同直接测序分型结果一致。将该系统应用于168份临床样本,经过统计学分析,用卡方检验发现高血压组和正常组AGT M 235T多态性存在显著差异(2χ=6.191,P<0.05),但ACE I/D多态性没有显著差异(χ2=5.241,P>0.05)。
基金the support of the Research Center for Advanced Materials Science(RCAMS)at King Khalid University Abha,Saudi Arabia,through Grant(KKU/RCAMS/22).
文摘Genetic polymorphism has a vital role in the pathogenesis and development of myocardial infarction(MI).Single nucleotide polymorphism at any one of the amino acid sequences can result in a diseased state.A single gene can exhibit genetic polymorphism at more than one position giving rise to different variants.Genetic polymorphism of angiotensinogen(AGT)M235T,AGT T174M,and angiotensin-1-converting enzyme(ACE)I/D,endothelial nitric oxide synthase(eNOS),and methylenetetrahydrofolate reductase(MTHFR)can be a risk factor for MI.However,it is important to study the prevalence of genetic polymorphisms of these genes among different populations.MI is influenced by genetic polymorphism of various genes,including AGT,ACE,eNOS,MTHFR,etc.However,the association of genetic polymorphism of these genes varies among different populations,but different ethnic groups could show contradictory results.These genes have shown a positive association with risks of MI in some populations,whereas the results have not been consistent with every ethnic group.In this article,we have summarized the genetic variations in the aforementioned genes and their association with MI.
文摘目的：探讨DNA损伤修复酶基因XRCC1Arg194Trp多态性和AGT基因第三外显子Leu84Phe多态性与食管癌易感性的关系。方法：采用病例-对照研究方法分析四川北部地区食管癌病例（n=155）和年龄、性别分布无差异的对照组（n=127）XRCC1基因Arg194Trp多态性和AGT基因第三外显子Leu84Phe多态性,两个基因多态的交互作用和基因多态与吸烟、饮酒之间的交互作用对食管癌易感性的影响。结果：XRCC1基因194位点各基因型在两组间的分布无统计学差异（χ~2=0.614;P=0.736）。AGT基因第三外显子第84位密码子各基因型在两组间的分布无统计学差异（χ~2=1.826;P=0.177）,吸烟、饮酒与AGT基因第三外显子第84位密码子突变基因型TT存在正交互作用,交互作用指数（the synergy index S,S）分别为7.375、17.67。结论：四川北部地区XRCC1基因194位点基因多态性与AGT基因第三外显子Leu84Phe多态性可能与食管癌的易感性无关,但AGT基因第三外显子Leu84Phe多态性可能与吸烟、饮酒与食管癌的易感性之间存在协同作用。
文摘The tumor selectivity of alkylating agents that produce guanine O6-chloroethyl (laromustine and carmustine) and O6-methyl (temozolomide) lesions depends upon O6-methylguanine-DNA methyltransferase (MGMT) activity being lower in tumor than in host tissue. Despite the established role of MGMT as a tumor resistance factor, consensus on how to assess MGMT expression in clinical samples is unsettled. The aim of this study is to examine the relationship between the values derived from distinctive MGMT measurements in 13, 12, 6 and 2 pairs of human tumors and matched normal adjacent tissue from the colon, kidney, lung and liver, respectively, and in human cell lines. The MGMT measurements included 1) alkyl-transfer assays using [benzene-3H]O6-benzylguanine as a substrate to assess functional MGMT activity, 2) methylation-specific PCR (MSP) to probe MGMT gene promoter CpG methylations as a measure of gene silencing, and 3) western immunoblots to analyze the MGMT protein. In human cell lines, a strict negative correlation existed between MGMT activity and the extent of promoter methylation. In tissue specimens, by contrast, the correlation between these two variables was low. Moreover, alkyl-transfer assays identified 3 pairs of tumors and normal tissue with tumor-selective reduction in MGMT activity in the absence of promoter methylation. Cell line MGMT migrated as a single band in western analyses, whereas tissue MGMT was heterogeneous around its molecular size and at much higher molecular masses, indicative of multi-layered post-translational modifications. Malignancy is occasionally associated with a mobility shift in MGMT. Contrary to the prevalent expectation that MGMT expression is governed at the level of gene silencing, these data suggest that other mechanisms that can lead to tumorselective reduction in MGMT activity exist in human tissue.
