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Identification of genes related to susceptibility of periodontal diseases and establishment of gene diagnosis

牙周病易感性相关基因的鉴定及基因诊断的建立

基本信息

批准号：
12470468
负责人：
WATANABE Hisashi
金额：
$ 9.22万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470468/
关键词：
Molecular diagnosis Hypophosphatasia Periodontal Disease Point mutation DNA expression vector Tissue non-specific alkaline phosphatase Mutant gene COS-1 cell 点突然変異

项目摘要

Hypophosphatasia (HOPS) is a clinically heterogeneous heritable disorder characterized by defective skeletal mineralization, deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity and premature loss of deciduous teeth. In a previous study, we found novel point mutations (F310L, V365I) in the TNSALP gene of a patient with severe periodontitis and childhood HOPS (J Periodontol, 1999). The V365I mutation was considered responsible for the inactive alkaline phosphatase (ALP) enzyme (J Bone Miner Res, 2002). We have characterized another ALP enzyme translated from the mutant F310L and compared it with the ALP in the patient's serum in the presenl study.The COS-1 cells transfected with the F310L and co-transfected with F310L and V365I exhibited a level of 67% and 31%, respectively with the enzymatic activity of the wild-type taken as 100%. After heating at 56℃ for 5 min, the residual activity of the wild-type, F310L and V365I exhibited a level of approximately 40.4%, 21.7% and 16.5% of unheated enzymatic activily, respectively. The ALP of patient's serum showed levamisol-nonresistant and heat labile as well as mutant ALP. This mutant might be responsible for the expression of symptoms of the childhood-type HOPS, in addition lo the mutant (V3651).

缺磷症（HOPS）是一种临床异质性遗传性疾病，其特征是骨骼矿化缺陷、组织非特异性碱性磷酸酶（TNSALP）活性缺乏和乳牙过早脱落。在之前的研究中，我们在一名患有严重牙周炎和儿童HOPS的患者的TNSALP基因中发现了新的点突变（F310L, V365I）（J Periodontol, 1999）。V365I突变被认为是导致碱性磷酸酶（ALP）酶失活的原因（J Bone Miner Res, 2002）。我们描述了从突变体F310L翻译的另一种ALP酶，并将其与本研究中患者血清中的ALP进行了比较。转染F310L和共转染F310L和V365I的COS-1细胞的酶活性分别为67%和31%，野生型的酶活性为100%。在56℃加热5 min后，野生型、F310L和V365I的剩余酶活性分别约为未加热酶活性的40.4%、21.7%和16.5%。患者血清ALP表现为左旋咪唑不耐药、热不稳定及突变型ALP。除了突变体（V3651）外，该突变体可能还负责儿童型HOPS症状的表达。