2型糖尿病易感位点的功能性L1逆转录转座子的研究  

Study of functional L1 retrotransposon in human type 2 diabetes susceptibility loci

作　　者：葛胜洁[1] 任跃忠[2] 徐荣臻[3] 

机构地区：[1]温州医学院附属第一医院内分泌科,325000 [2]浙江大学医学院附属第二医院内分泌科 [3]浙江大学医学院附属第二医院临床实验中心

出　　处：《中华医学遗传学杂志》2003年第4期287-291,共5页Chinese Journal of Medical Genetics

摘　　要：目的　通过一种新的策略寻找 2型糖尿病的易感基因。方法　应用美国生物技术信息中心提供的 BL AST(basic local alignmentsearch tool)检索工具 ,对已报道的 2型糖尿病易感位点的核酸序列进行检索分析 ,发现功能性 L1逆转录转座子可能是易感基因。然后应用逆转录 -聚合酶链反应检测 2 5例 2型糖尿病患者和 2 2名正常对照的 L1逆转录转座子表达水平 ,用 SPSS10 .0软件包进行统计学分析 ,并对6例患者和 4名正常人的 L 1逆转录转座子进行定位克隆、基因组序列测定。结果　对人类基因组及 Gen-Bank数据库进行全面搜索分析发现 L 1逆转录转座子分布在除 19号、2 1号和 Y染色体外的其它染色体上。这种分布情况与已报道的易感位点在染色体上的分布情况有相似性。功能性 L1逆转录转座子在 2型糖尿病患者组的表达水平明显低于正常对照组 (P<0 .0 0 1)。L1逆转录转座子在 2型糖尿病患者有不同程度的缺失和 (或 )无意义突变 ,而在正常对照无突变。结论　功能性 L1逆转录转座子可能是 2型糖尿病的某一易感基因或者是其易感基因的重要调节因子之一。功能性 L 1逆转录转座子表达水平的高低可能可以作为筛选 2型糖尿病的一个生物学指标。Objective: To investigate the susceptibility gene of type 2 diabetes mellitus (T2DM) through a novel strategy. Methods: Firstly, the common feature of the putative susceptibility genes in the reported susceptibility loci was searched by using NCBI BLAST, and a functional L1 retrotransposon in the loci was found. Secondly, the mRNA expression level of the functional L1 retrotransposon in 25 Han T2DM patients and 22 normal controls was investigated by reverse transcription-polymerase chain reaction, and statistical analysis was implemented in statistical package SPSS10. 0. Thirdly, L1 retrotransponson genome mutation screening was performed via sequencing. Results: Screening the human genome for the retrotransposon genome via alignment with the L1 genome using NCBI BLAST showed the functional L1 retrotransposons distribute on most chromosomes except for chromosomes 19, 21 and Y on which rare type 2 diabetes susceptibility loci were reported to reside, and their distribution sites are consistent with the locations of the reported candidate type 2 diabetes susceptibility loci. The mRNA expression level of the functional L1 retrotransposon in the T2DM patients was significantly lower than that in normal subjects (P < 0.001). Nonsense mutations including deletion and/or point mutations were observed in all of the 6 T2DM patients tested, but no mutation was observed in all of the 4 normal controls tested. Conclusion: The functional L1 retrotransposon may be a candidate susceptibility gene of type 2 diabetes or a key regulator of the susceptibility genes, and it may be an ideal candidate biomarker for screening type 2 diabetes.

关 键 词：2型糖尿病 易感基因 功能性L1逆转录转座子 逆转录-聚合酶链反应 

分 类 号：R587.1[医药卫生—内分泌]