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Journal of Lipid Research, Vol. 42, 620-630, April 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Apolipoprotein L gene family: tissue-specific expression, splicing, promoter regions; discovery of a new gene

Correspondence to: Philippe N. Duchateau, To whom correspondence should be addressed.

Previously we identified and cloned the cDNA for a new protein, apolipoprotein L (apoL), present in plasma and mainly associated with large high density lipoprotein particles. Using 5' rapid amplification of cDNA ends, RT-PCR and comparison with three Human Genome Project and three expressed sequence tag sequences, we have characterized the gene for apoL and for three additional, highly homologous proteins that constitute a new family of proteins that display no homology with previously described apolipoproteins. The genes for all four proteins, apoL-I, apoL-II, apoL-III, and apoL-IV, are located at chromosome 22q12.1-13.1 within a 127,000-bp region. The apoL-I gene is in the opposite orientation to the other three. All four genes have TATA-less promoters, which contain putative sterol regulatory elements, suggesting that transcription of these genes may be coordinated with that of the low density lipoprotein receptor and genes in pathways involving the synthesis of triglycerides and cholesterol. The gene family has a consensus eight-exon structure with alternative splice sites that could produce as many as eight distinct gene products. The apoL-II and apoL-III genes have alternative transcriptional start sites as a result of additional 5' exons. apoL-I, apoL-II, and apoL-III are expressed to the highest degree in the lung. Other tissues with high expression are the pancreas, prostate, spleen, liver, and placenta.

Four clustered common polymorphisms, three of which altered the protein sequence, were found in apoL-I, all in linkage disequilibrium, and describing two haplotypes: the more common Lys₁₆₆/Ile₂₄₄/Lys₂₇₁ and the rarer Glu₁₆₆/Met₂₄₄/Arg₂₇₁.—Duchateau, P. N., C. R. Pullinger, M. H. Cho, C. Eng, and J. P. Kane. Apolipoprotein L gene family: tissue-specific expression, splicing, promoter regions; discovery of a new gene. J. Lipid Res. 2001. 42: 620;–630.

Supplementary key words: HDL, alternative splicing, lipoprotein, chromosome 22

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