Background Epidemiological studies have shown that low levels of plasma high density lipoprotein (HDL) cholesterol are associated with increased risk of ischemic heart disease (IHD), but it appears that genetic forms of low HDL cholesterol levels, as opposed to lifestyle-induced low levels of HDL cholesterol, do not result in increased risk of IHD. Therefore, the etiology of reduced levels of plasma HDL cholesterol may represent a factor that should be considered in risk stratification with respect to primary prevention. Genes encoding proteins involved in HDL metabolism, such as the ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes for harboring mutations that lead to low HDL cholesterol levels. Methods The ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol level of 0.53 (± 0.15) mmol/l, were subjected to DNA sequencing. Results Several mutations were identified in the ABCA1 gene, and two mutations were identified in the apoA-I gene. A total of 18 patients (32%) were carriers of mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45 (± 0.15) mmol/l compared to 0.57 (± 0.14) mmol/l in noncarriers (p Conclusion Mutations in the genes encoding ABCA1 and apoA-I are common in Norwegians, with a markedly decreased HDL cholesterol level.
