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.