Kuriki Chikako, Tanaka Takao, Fukui Yuka, Sato Osamu, Motojima Kiyoto
Department of Biochemistry, School of Pharmaceutical Sciences, Toho University, Chiba, Japan.
Biol Pharm Bull. 2002 Nov;25(11):1476-8. doi: 10.1248/bpb.25.1476.
FAT/CD36 is involved in various processes including uptake of fatty acid into the heart and of oxidized low density lipoprotein (LDL) into macrophages. Expression of the FAT/CD36 gene is regulated in a tissue-specific manner, and loss or inadequately regulated expression of FAT/CD36 is thought to be one of the causes of some diseases such as cardiomyopathy and atherosclerosis. We recently found that the mouse and human FAT/CD36 genes have two independent promoters. To elucidate the physiological significance of the two promoters, we characterized the peroxisome proliferator-activated receptor ligand-responsive new promoter that is located 14 kb upstream of the previously reported promoter of the human gene. We found several SNPs in this region some of which were found only when analyzing DNA samples from the patients lacking FAT/CD36 totally or in a cell-type-specific manner. However, we could not detect any negative effect of these SNPs on the transcription by transient transfection analysis, suggesting that the identified SNPs alone are not directly linked to low transcriptional activities.
FAT/CD36参与多种过程，包括脂肪酸进入心脏以及氧化型低密度脂蛋白（LDL）进入巨噬细胞。FAT/CD36基因的表达以组织特异性方式受到调控，FAT/CD36的缺失或表达调控不当被认为是心肌病和动脉粥样硬化等一些疾病的病因之一。我们最近发现小鼠和人类的FAT/CD36基因有两个独立的启动子。为了阐明这两个启动子的生理意义，我们对位于人类基因先前报道的启动子上游14 kb处的过氧化物酶体增殖物激活受体配体响应新启动子进行了表征。我们在该区域发现了几个单核苷酸多态性（SNP），其中一些仅在分析完全缺乏FAT/CD36或以细胞类型特异性方式缺乏FAT/CD36的患者的DNA样本时才被发现。然而，通过瞬时转染分析，我们未检测到这些SNP对转录有任何负面影响，这表明所鉴定的SNP单独并不直接与低转录活性相关。
