Niemann-Pick type C1-like 1 (NPC1L1) protein is responsible for intestinal cholesterol absorption. The aim of the study was to identify genetic polymorphisms of the NPC1L1 gene as well as their functional significance. The method involved screening of promoter and coding regions of the NPC1L1 gene for genetic polymorphisms by direct DNA sequencing of genomic DNA from 50 individuals. Functional studies on promoter polymorphisms were performed using luciferase assay. Association between the polymorphisms and serum cholesterol levels were investigated in 224 individuals. The results showed that in total, 11 single nucleotide polymorphisms were identified. Among them, a promoter polymorphism, g.À762T4C, and a synonymous polymorphism, g.1679C4G, were common (34 and 36%, respectively). These two polymorphisms were highly linked (D¢ value¼0.7459, P-value o0.00001). For the g.À762T4C promoter polymorphism, luciferase assay in HepG2 cell line demonstrated that the À762C allele had a significantly higher promoter activity than the À762T allele (1.30 ± 0.22 vs 0.37 ± 0.06, 3.5-fold, Po0.05). We also showed that the NPC1L1 promoter activity was downregulated by cholesterol content in both genotypes. When association studies were performed, we found that À762C allele was associated with significantly higher serum total cholesterol and LDL-cholesterol content levels in a recessive model (LDL-cholesterol value¼131.2 ± 8.1 vs 116.4 ± 2.2 mg dl -1 ; total cholesterol value¼214.7 ± 9.0 mg dl -1 vs 196.9 ± 2.6, P-value o0.05, n¼224). In conclusion, the C allele at À762 position of the NPC1L1 gene was common in people of Chinese ethnicity. The À762C allele had a higher promoter activity and was associated with a higher serum total cholesterol and LDL-cholesterol level.

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