Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measu...Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measured by a two-step [α-32P]-dCTP incorporated asymmetric polymeric chain reaction (PCR), and the (CAG)n repeats of both malignant and nonmalignant prostate cells in fixed paraffin-embedded tissue (PET) specimen from 36 case of PCa were determined by sequence analysis. Results: The repeats of polymorphic (CAG) n among normal men ranged from 11 to 29, and the most frequent repeat was 22(18. 69%), with 23(14. 02%), 24(10. 28%) and 21(10. 28%) being less frequent. The (CAG)n repeats of malignant prostate cells equaled to that of nonmalignant adjacent prostate tissue cells from the same PET specimen in all 36 PCa, and the (CAG)n repeats in 36 PCa which ranged from 16 to 22 were shorter than that in normal males significantly (P<0. 05), while no significant difference in (CAG)n repeats among various grade of tumor's differentiation (well-differentiated, intermediate-differentiated and poor-differentiated) was found (P>0. 05). Conclusion; The present study suggest that short hAR gene (CAG)n micro-satellite might be associated with the occurrence of PCa, but not with the differentiation of PCa.展开更多
目的:脊髓小脑共济失调2型(spinocerebellar ataxia type 2,SCA2)是世界上最常见的常染色体显性遗传的共济失调之一。多篇报道显示某些含polyQ基因的CAG重复序列可能影响SCA2患者的发病年龄(age at onset,AAO),但在中国SCA2患者中进行...目的:脊髓小脑共济失调2型(spinocerebellar ataxia type 2,SCA2)是世界上最常见的常染色体显性遗传的共济失调之一。多篇报道显示某些含polyQ基因的CAG重复序列可能影响SCA2患者的发病年龄(age at onset,AAO),但在中国SCA2患者中进行研究的较少。因此,本研究旨在探讨CAG重复序列的长度对中国SCA2患者AAO的影响。方法:纳入119例SCA2患者,根据其主要表型分为2组:17例来自9个帕金森综合征家庭的SCA2患者作为帕金森病-SCA2(Parkinson.s disease-SCA2,PD-SAC2)组,91例来自66个SCA2家庭和11例散发的SCA2患者作为共济失调-SAC2(ataxia-SCA2,A-SCA2)组。使用荧光PCR筛查ATXN2和其他含m6(CAG)n基因中CAG重复序列的长度。采用Spearman.s等级相关的方法分析含m6(CAG)n基因中CAG重复序列的长度与AAO的相关性,采用回归分析评估CAG重复序列的长度对AAO变异的贡献,采用t检验比较PD-SAC2组与A-SCA2组间含m6(CAG)n基因中CAG重复序列的长度。结果:ATXN2基因中含较长CAG重复序列的等位基因的CAG重复序列的长度与SCA2的AAO呈负相关(R=-0.251,P<0.05),可解释41.7%的AAO变异。AAO与ATXN7基因中含较短CAG重复序列的等位基因(R=-0.251,P=0.006)及TBP基因中含较长CAG重复序列的等位基因(R=-0.197,P=0.034)的CAG重复序列的长度均呈负相关。在携带含CAG重复序列的ATXN3、CACNA1A、ATXN7、TBP和RAI1基因的SCA2患者中也检测到AAO延迟的趋势。此外,ATXN7基因和ATXN2基因的CAG重复序列的长度在A-SCA2组和PD-SCA2组之间的差异有统计学意义(均P<0.05)。结论:ATXN2中的CAG重复序列是影响中国SCA2患者AAO的主要遗传因素。ATXN3、CACNA1A、ATXN7、TBP和RAI1基因的CAG重复序列的长度可能是与SCA2的AAO相关的因素。ATXN7基因中的CAG重复序列的长度可能是SCA2患者表现为帕金森综合征的影响因素之一。展开更多
基金Supported by the National Natural Science Foundation of China (No. 39670300)
文摘Objective: To study the relationship between the polymorphic (CAG)n micro-satellite of human androgen receptor (hAR) gene and prostate cancer (PCa). Methods: The number of (CAG)n repeats in 107 normal males were measured by a two-step [α-32P]-dCTP incorporated asymmetric polymeric chain reaction (PCR), and the (CAG)n repeats of both malignant and nonmalignant prostate cells in fixed paraffin-embedded tissue (PET) specimen from 36 case of PCa were determined by sequence analysis. Results: The repeats of polymorphic (CAG) n among normal men ranged from 11 to 29, and the most frequent repeat was 22(18. 69%), with 23(14. 02%), 24(10. 28%) and 21(10. 28%) being less frequent. The (CAG)n repeats of malignant prostate cells equaled to that of nonmalignant adjacent prostate tissue cells from the same PET specimen in all 36 PCa, and the (CAG)n repeats in 36 PCa which ranged from 16 to 22 were shorter than that in normal males significantly (P<0. 05), while no significant difference in (CAG)n repeats among various grade of tumor's differentiation (well-differentiated, intermediate-differentiated and poor-differentiated) was found (P>0. 05). Conclusion; The present study suggest that short hAR gene (CAG)n micro-satellite might be associated with the occurrence of PCa, but not with the differentiation of PCa.
基金supported by the National Key Research and Development Program(2018YFC1312003)the National Natural Science Foundation(81671120,81300981)+2 种基金the Natural Science Foundation for Distinguished Young Scholars of Hunan Province(2020JJ2057)the Degree&Postgraduate Education Reform Project of Central South University(2020JGB136)the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital)(2020LCJJ13),China。
文摘目的:脊髓小脑共济失调2型(spinocerebellar ataxia type 2,SCA2)是世界上最常见的常染色体显性遗传的共济失调之一。多篇报道显示某些含polyQ基因的CAG重复序列可能影响SCA2患者的发病年龄(age at onset,AAO),但在中国SCA2患者中进行研究的较少。因此,本研究旨在探讨CAG重复序列的长度对中国SCA2患者AAO的影响。方法:纳入119例SCA2患者,根据其主要表型分为2组:17例来自9个帕金森综合征家庭的SCA2患者作为帕金森病-SCA2(Parkinson.s disease-SCA2,PD-SAC2)组,91例来自66个SCA2家庭和11例散发的SCA2患者作为共济失调-SAC2(ataxia-SCA2,A-SCA2)组。使用荧光PCR筛查ATXN2和其他含m6(CAG)n基因中CAG重复序列的长度。采用Spearman.s等级相关的方法分析含m6(CAG)n基因中CAG重复序列的长度与AAO的相关性,采用回归分析评估CAG重复序列的长度对AAO变异的贡献,采用t检验比较PD-SAC2组与A-SCA2组间含m6(CAG)n基因中CAG重复序列的长度。结果:ATXN2基因中含较长CAG重复序列的等位基因的CAG重复序列的长度与SCA2的AAO呈负相关(R=-0.251,P<0.05),可解释41.7%的AAO变异。AAO与ATXN7基因中含较短CAG重复序列的等位基因(R=-0.251,P=0.006)及TBP基因中含较长CAG重复序列的等位基因(R=-0.197,P=0.034)的CAG重复序列的长度均呈负相关。在携带含CAG重复序列的ATXN3、CACNA1A、ATXN7、TBP和RAI1基因的SCA2患者中也检测到AAO延迟的趋势。此外,ATXN7基因和ATXN2基因的CAG重复序列的长度在A-SCA2组和PD-SCA2组之间的差异有统计学意义(均P<0.05)。结论:ATXN2中的CAG重复序列是影响中国SCA2患者AAO的主要遗传因素。ATXN3、CACNA1A、ATXN7、TBP和RAI1基因的CAG重复序列的长度可能是与SCA2的AAO相关的因素。ATXN7基因中的CAG重复序列的长度可能是SCA2患者表现为帕金森综合征的影响因素之一。
