A SNP of NPC1L1 affects cholesterol absorption in Japanese.
A SNP of NPC1L1 affects cholesterol absorption in Japanese.
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DOI：
10.5551/jat.2451
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发表时间：
2010-04
影响因子：
4.4
通讯作者：
T. Maeda;A. Honda;Toshio Ishikawa;M. Kinoshita;Yamato Mashimo;Yoko Takeoka;Daijiro Yasuda;J. Kusano;K. Tsukamoto;Y. Matsuzaki;T. Teramoto
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文献类型：
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作者：
T. Maeda;A. Honda;Toshio Ishikawa;M. Kinoshita;Yamato Mashimo;Yoko Takeoka;Daijiro Yasuda;J. Kusano;K. Tsukamoto;Y. Matsuzaki;T. Teramoto
目的依折麦布作用于肠胆固醇吸收的关键蛋白NPC 1 L1，降低血清低密度脂蛋白胆固醇（LDL-C）水平。据报道，依折麦布对血清LDL-C水平的反应在NPC 1 L1单倍型之间存在差异。我们分析了日本人的NPC 1 L1基因型，并研究了基因型之间胆固醇合成/吸收标志物的差异。方法采用液相色谱-串联质谱法（LC-MS/MS）测定42名健康志愿者的血胆固醇合成标志物（胆甾醇）和吸收标志物（谷甾醇和菜油甾醇）。基于加拿大Hegele RA等人的研究，我们选择了三个SNP（1735 C>G，25342 A>C和27677 T>C（相对于转录起始位点的数字）），并使用PCR-RFLP对其进行分析。结果1735 C/G（46%）>C/C（35%）>G/G（19%），25342 A/A（97%）>A/C（3%）>C/C（0%），27677 T/T（97%）>T/C（3%）>C/C（0%）。1735 G/G组血清菜油甾醇水平显著高于1735 C/G+C/C组，但不同基因型间的岩藻甾醇水平无显著差异。结论我们的研究结果揭示了日本人和加拿大人NPC 1 L1多态性频率的差异。在日本，与1735 C/G+C/C组相比，1735 G/G组显示出肠胆固醇吸收增强。
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.