Polymorphisms of the Niemann-Pick C1-like 1 gene in a Japanese population.

The Niemann-Pick C1 like 1 (NPC1L1) protein is a polytopic transmembrane protein responsible for dietary cholesterol absorption. Genetic variation in the gene affects cholesterol absorption and serum cholesterol levels. However, genotypes have not previously been invesigated. In this study, genotyping of the gene was examined in healthy individuals as well as patients with hepatitis C virus (HCV) and inflammatory bowel disease (IBD). A total of 541 individuals were enrolled in the study, including 80 patients with HCV hepatitis, 205 with ulcerative colitis (UC) and 127 with Crohn's disease (CD). Genotyping was performed using TaqMan SNP assays. Minor allelic frequencies of the 17345C>G (rs2072183) and 19031G>A (rs4720470) SNPs were found to be 0.40 and 0.30, respectively. No significant differences were detected in serum HCV levels in the 1735C>G or 19031G>A SNPs. The 1735C>G SNPs were not associated with total cholesterol (TC) levels in the healthy controls and/or HCV patients. However, statistically significant associations between the 1735GG variant and TC levels were detected in CD patients, with 1735GG carriers having the highest TC levels compared to the 1735CC and 1735CG carriers (P=0.048). Similar trends were noted in UC patients, but did not reach statistical significance (P= 0.19). The 19031G>A SNPs were not associated with TC levels in the healthy controls or patients. This study showed the allelic and genotypic distribution of 1735C>G and 19031G>ASNPs of the gene in a large number of subjects. The NPC1L1 1735GG variant may therefore be favorable for CD accompanied with malnutrition.