Analysis of hABC1 gene 5 ' end: Additional peptide sequence, promoter region, and four polymorphisms

Evidence linking mutations in ATP-binding-cassette transporter gene 1 (ABC1 ) to Tangier disease suggests it functions in the active transport of free cholesterol out of cells. Since its mRNA level is regulated in response to cellular cholesterol stores it is of interest to explore its promoter respo nse elements, and to investigate polymorphisms for their contributions to t he prevalence of low levels of HDL in the population that promotes prematur e coronary heart disease. Investigation of the 5' end of the gene by 5' RAC E analysis revealed 455 nucleotides additional to published sequences, and predicts another 60 amino acid N-terminal residues, resulting in a 2261-res idue protein. Protein sequence analysis predicts a membrane-spanning region and possible signal peptide. The 5' flanking region was located by a Human Research Project BLAST search. This region contains regulatory elements th at potentially control ABC1 gene expression. In addition to numerous SP1 bi nding sites there are four putative sterol regulatory elements (SREs). Our studies uncovered three single nucleotide substitution polymorphisms, one i n the promoter region and two in the 5' untranslated region (5'UTR), plus a n insertion/deletion polymorphism, (C) 2000 Academic Press.