| A SNP of NPC1L1 affects cholesterol absorption in Japanese. | |
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MedLine Citation:
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PMID: 20379057 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: Ezetimibe is known to target Niemann-Pick Type C1 Like1 (NPC1L1), a key protein in intestinal cholesterol absorption, and thus to decrease serum LDL-cholesterol (LDL-C) levels. The response of serum LDL-C levels to ezetimibe was reported to differe among NPC1L1 haplotypes.We analyzed NPC1L1 genotypes in Japanese and investigated differences in markers of cholesterol synthesis/absorption among the genotypes. METHODS: Blood samples were collected from 42 adult volunteers to measure markers of cholesterol synthesis (lathosterol) and absorption (sitosterol and campesterol) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on a study by Hegele RA et al. in Canada, we selected three SNPs (1735 C>G, 25342 A>C and 27677 T>C (numbers relative to the transcription start site)) and analyzed them using PCR-RFLP. RESULTS: The frequencies of genotypes were as follows: 1735 C/G (46%)>C/C (35%)>G/G (19%), 25342 A/A (97%)>A/C (3%)>C/C (0%) and 27677 T/T (97%)>T/C (3%)>C/C (0%). Serum campesterol levels were significantly higher in the 1735 G/G group than 1735 C/G+C/C group, but lathosterol levels showed no significant differences between the genotypes. CONCLUSION: Our results revealed differences in the frequency of the NPC1L1 polymorphism between Japanese and Canadians. In Japanese, the 1735 G/G group showed enhanced cholesterol absorption from the intestine, as compared to the 1735 C/G+C/C group. |
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Authors:
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Tomomi Maeda; Akira Honda; Toshio Ishikawa; Makoto Kinoshita; Yamato Mashimo; Yoko Takeoka; Daijiro Yasuda; Jun Kusano; Kazuhisa Tsukamoto; Yasushi Matsuzaki; Tamio Teramoto |
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Publication Detail:
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Type: Journal Article Date: 2010-04-07 |
Journal Detail:
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Title: Journal of atherosclerosis and thrombosis Volume: 17 ISSN: 1880-3873 ISO Abbreviation: J. Atheroscler. Thromb. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-05-10 Completed Date: 2010-08-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9506298 Medline TA: J Atheroscler Thromb Country: Japan |
Other Details:
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Languages: eng Pagination: 356-60 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. a.fenton@liverpool.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Asian Continental Ancestry Group / genetics* Cholesterol / blood* Chromatography, Liquid Female Genotype Humans Intestines / metabolism* Male Membrane Proteins / genetics* Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Polymorphism, Single Nucleotide / genetics* Tandem Mass Spectrometry |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 0/NPC1L1 protein, human; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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