A SNP of NPC1L1 Affects Cholesterol Absorption in Japanese

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.