Structural and functional analysis of a new upstream promoter of the human FAT/CD36 gene.

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.