The human apM-1, an adipocyte-specific gene linked to the family of TNF's and to genes expressed in activated T cells, is mapped to chromosome 1q21.3-q23, a susceptibility locus identified for familial combined hyperlipidaemia (FCH)

The human adipocyte-specific apM-1 gene encodes a secretory protein of the adipose tissue that has been suggested to play a role in the pathogenesis o f obesity. The regulation of apM-1 was studied along adipocyte differentiat ion. While apM-1-mRNA and apM-1 protein were absent in preadipocytes and in 48 h differentiated adipocytes, they were found upregulated from day 4 to day 9 of adipocyte differentiation as shown by RNase protection assay and W estern blot analysis. These data indicate that apM-1 may be a late marker o f adipocyte differentiation, In human sera apM-1 protein is also detectable by Western blots using a polyclonal antibody raised against a synthetic pe ptide sequence of the human apM-1. The genomic structure of the human apM-1 gene together with a total of 2.7 kb of the 5'-flanking region with putati ve transcription factor binding sites is presented. Interestingly, sequence comparisons link the apM-1 gene to tbe family of TNF's and to genes expres sed in activated T-cells. The chromosomal localization of apM-1 was investi gated by FISH and mapped to human chromosome 1q21.3-1q23, a region that was identified as a susceptibility locus for Familial Combined Hyperlipidaemia (FCH) and polygenic NIDDM. These data and the chromosomal localization on chromosome 1q21.3-q23 raises the possibility that apM-1 as an adipocyte-spe cific secretory protein may play a rob in the pathogenesis of FCH and assoc iated insulin resistance. Exon- and intronspecific primer sequences are pre sented as a basis for mutation screening of patients affected with FCH. (C) 1999 Academic Press.