Study on the structure of gene of histamine inactivating enzyme and its regulation of expression

1.人组胺N-甲基转移酶（HMT）基因结构的研究我们用人HMT cDNA筛选人基因组文库（EMBL 3），获得了多个基因组克隆，并对其结构进行了测定。此外，我们分析了一个转录点的引物延伸方法与nRNA提取的人肾。结果表明，引物延伸法检测到2条主带。基于下游转录点的HMT基因结构分析表明，人HMT基因由6个外显子组成，第一外显子含有一个137 b的编码区和一个相对较长的383 b的非编码区。在转录点上游2kb区域不存在TATA样序列，但检测到3个SP-1、5个加塔、2个LRF-1、5个LBP-1结合序列。另一方面，由于另一个主要转录点位于另一个转录点上游约100 b处，因此有可能期待新的第一外显子。正如在其他基因中所报道的那样，推测可能的交替基因是一种新的基因。 ...更多信息 2. HMT基因的多态性根据我们以前的报道和R Weishilboum的报道，在编码区的核苷酸序列上有两个变化。密码子105内的核苷酸314是T或C，产生编码异亮氨酸或苏氨酸的密码子。密码子199内的核苷酸595是A或G，产生异亮氨酸或缬氨酸。此外，我们还发现了第一外显子第89位核苷酸缺失8个核苷酸（CTAACAAA）的克隆。此外，第6外显子附近的CA重复序列是多态性的，我们分析了100名正常人的CA重复数。结果表明，CA重复数分布在15 ~ 30之间，可以作为HMT基因多态性的一个有用的标记。3. HMT基因与支气管哮喘的遗传连锁气道高反应性是支气管哮喘的一个关键因素，已被认为是遗传性的生理特征之一。HMT活性水平与豚鼠气道对组胺的收缩反应密切相关。在这方面，为了检验HMT基因是否与支气管哮喘有关，我们比较了哮喘患者和正常人的多态性。结果表明，CA重复数的分布与正常个体有显著差异。特别是CA重复数小于20可能是支气管哮喘的危险因素。少

1.Gene structure of human histamine N-methyltransferase (HMT)We obtained several genomic clones by screening human genomic library (EMBL3) with human HMT cDNA and determined its structure. In addition, we analyzed a transcriptional point by a primer extension method with nRNA extracted from human kidney. As a result, the experiment of primer extension method revealed that 2 major bands was detected. According to an analysis of HMT gene structure based on the transcriptional point locating downstream, human HMT gene consists of 6 exons, and the first exon contains a 137b coding region and a realtively long 383b noncoding region. While TATA-like sequence did not exist in 2kb region upstream to a transcriptional point, 3SP-1,5 GATA,2 LRF-1,5 LBP-1binding sequence were detected. On the other hand, since another major transcriptional point located about 100b upstream to other one, it is possible to expect a new first exon. As reported in other genes, it was speculated that possible alternat … More ive transcriptional points were involved in a tissue-specific expression.2.Polymorphism of HMT geneTo date, sccording to our previous report and the report by R Weishilboum, two changes of nucleotide sequence in coding region. Nucleotide 314 within codon 105 is a T or a C,resulting in codons that encode isoleucine or threonine. Nucleotide 595 within codon 199 is an A or G,resulting isoleucine or valine. In addition, we found clones which lack of 8 nuleotides (CTAACAAA) in ncleotide 89 of first exon. Furthermore CA repeat sequense near 6th exon was polymorphic and we analyzed the number of CA repeat among 100 normal individuals. As a result, CA repeat number distributed from 15 to 30 and was thought to be a useful marker of polymorphism of HMT gene.3.Genetic linckage of HMT gene to bronchial asthmaThe airway hyperresponsiveness, a critical factor of bronchial asthma, has been recognized as one of physical characteristics inherited genetically. The level of HMT activity is closely associated with airway contractile response to histamine in guinea pigs. In this regard, to examine whether HMT gene is linked to bronchial asthma, we compared polymorphism of asthmatics to that of normal individuals. As a result, the distribution of CA repeat number was significantly different from that of normal individuals. Especially, CA repeat size smaller than 20 seemed to be a risk factor for bronchial asthma. Less