Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene

We have reported the cDNA cloning of a modified low-density-lipoprotein (LD L) receptor, designated lectin-like oxidized LDL receptor-1 (LOX-1), which is postulated to be involved in endothelial dysfunction and the pathogenesi s of atherosclerosis. Here, we determined the organization of the human LOX -1 gene, including the 5'-regulatory region. The 5'-regulatory region conta ined several potential cis-regulatory elements, such as GATA-2 binding elem ent, c-ets-l binding element: 12-O-tetradecanoylphorbol 13-acetate-responsi ve element and shear-stress-responsive elements, which may mediate the endo thelium-specific and inducible expression of LOX-1. The major transcription -initiation site was found to be located 29 nucleotides downstream of the T ATA box and 61 nucleotides upstream from the translation-initiation codon, The minor initiation site was found to be 5 bp downstream from the major si te. Most of the promoter activity of the LOX-1 gene was ascribed to the reg ion (-150 to -90) containing the GC and CAAT boxes. The coding sequence was divided into 6 exons by 5 introns. The first 3 exons corresponded to the d ifferent functional domains of the protein (cytoplasmic, transmembrane and neck domains), and the residual 3 exons encoded the carbohydrate-recognitio n domain similar to the case of other C-type lectin genes. The LOX-1 gene w as a single-copy gene and assigned to the p12.3-p13.2 region of chromosome 12. Since the locus for a familial hypertension has been mapped to the over lapping region, LOX-1 might be the gene responsible for the hypertension.