Key result
ABCA1 missense mutations correlate with clinical lipid phenotypes based on specific functional defect severity.
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Mutations in ATP-binding cassette transporter A1 (ABCA1) cause Tangier disease and familial hypoalphalipoproteinemia, resulting in low to absent plasma high-density lipoprotein cholesterol levels. However, wide variations in clinical lipid phenotypes are observed in patients with mutations in ABCA1. We hypothesized that the various lipid phenotypes would be the direct result of discrete and differing effects of the mutations on ABCA1 function. To determine whether there is a correlation between the mutations and the resulting phenotypes, we generated in vitro 15 missense mutations that have been described in patients with Tangier disease and familial hypoalphalipoproteinemia. Using localization of ABCA1, its ability to induce cell surface binding of apolipoprotein A-I, and its ability to elicit efflux of cholesterol and phospholipids to apolipoprotein A-I we determined that the phenotypes of patients correlate with the severity and nature of defects in ABCA1 function.
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Singaraja et al. (2006) studied Tangier disease and familial hypoalphalipoproteinemia. 15 missense mutations in ABCA1 was evaluated on ABCA1 localization, cell surface binding of apolipoprotein A-I, and cholesterol/phospholipid efflux to apolipoprotein A-I. Fifteen missense mutations in ABCA1 generated in vitro showed that patient clinical lipid phenotypes correlate with the severity and nature of defects in ABCA1 function.
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