Purpose: Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects reported in heterozygous state regard plasma HDL, cell cholesterol efflux and coronary artery disease. We investigated whether in vitro replicative skin fibroblast senescence shown in TD proband (Horn), his father (Het), and in a healthy control might be induced in a "gene-dosage way". Methods: Senescence was evaluated by staining test for p-Galactosidase and telomere length (TL) on fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density lipoprotein receptor) gene expression was also evaluated. Results: Horn cells showed early senescent morphology and reduced growth at all passages in vitro. The cell positive percentage for p-Galactosidase test was highly increased in Horn compared to Het cells at late replicative status (66.1% vs 41.3% respectively). TL was significantly shorter at high stage either in Horn (p < 0.0001) or in Het (p < 0.005). At early replication cycles ABCG1 gene expression was about 3-fold higher in Horn compared to Het cells (0.44 vs 0.14 arbitrary unit). Conclusions: ABCA1 gene mutation may have "gene-dosage way" effect on in vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene expression could highlight a role of ABCA1 on cytoskeleton regulation associated to cell cholesterol metabolism. (C) 2014 Elsevier Inc. All rights reserved.