@article{oai:air.repo.nii.ac.jp:00001755,
 author = {Hirai, Daishi and Narita, Ayuko and Takahashi, Tsutomu},
 issue = {3/4},
 journal = {秋田医学},
 month = {Mar},
 note = {Types A and B Niemann-Pick disease (NPD) comprise an autosomal recessive disorder caused by a deficiency of lysosomal acid sphingomyelinase (ASM), which leads to the intracellular accumulation of sphingomyelin and cholesterol and results in abnormalities of lipid metabolism. We report two patients with types A and B NPD showing low levels of high-density lipoprotein (HDL) cholesterol in their sera. Three novel mutations, c.567delT, c.575delC, and c.1481-9T>G, and a known mutation, c.691T>C, of the ASM gene were identified in the patients. The c.691T>C mutation is a unique genotype related to a very mild phenotype of type B NPD in the Japanese population. Next, the mRNA expressions of 4 ATP-binding cassette (ABC) transporters related to lipid metabolism, ABCA1, ABCA3, ABCA7, and ABCG1, were analyzed in fibroblasts with types A and B NPD by real-time RT-PCR using hybridization probes. In the analyses, the mRNA levels of ABCG1 were significantly decreased in the fibroblasts of types A and B NPD. The decreased protein level of ABCG1 was also confirmed by Western blot in a fibroblast of type B NPD. The results suggest that secondary dysfunction of ABCG1 may cause an impairment of cholesterol efflux in the peripheral cells, leading to the low plasma levels of HDL cholesterol in types A and B NPD. ABCG1 is a liver-X-receptor (LXR) target gene involved in cholesterol efflux to HDL, therefore LXR agonist treatment resulted in the reduction of cholesterol and sphingomyelin storage in the fibroblasts of type B NPD.},
 pages = {123--133},
 title = {ATP-BINDING CASSETTE (ABC) TRANSPORTER GENESIN FIBROBLASTS WITH TYPES A AND B NIEMANN-PICK DISEASE},
 volume = {37},
 year = {2011}
}