A SNP of NPC1L1 affects cholesterol absorption in Japanese.
OBJECTIVE
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.


CONCLUSIONS
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.
Maeda
Tomomi
T
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. a.fenton@liverpool.ac.uk
Honda
Akira
A
Ishikawa
Toshio
T
Kinoshita
Makoto
M
Mashimo
Yamato
Y
Takeoka
Yoko
Y
Yasuda
Daijiro
D
Kusano
Jun
J
Tsukamoto
Kazuhisa
K
Matsuzaki
Yasushi
Y
Teramoto
Tamio
T
D000328:Adult; D044466:Asian People / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D002853:Chromatography, Liquid; D005260:Female; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053719:Tandem Mass Spectrometry
D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D002784:Cholesterol