Analysis of nsSNP rs1468384 of NPC1L1 and its association with plasma cholesterol levels in general population

Niemann-Pick C1 �like 1 (NPC1L1) protein, a newly identified sterol influx transporter, located at the apical membrane of the enterocyte, which may actively facilitate the uptake of cholesterol by promoting the passage of sterols across the brush border membrane of the enterocyte. It effects intestinal cholesterol absorption and intracellular transport and as such is an integral part of complex process of cholesterol homeostasis. The study of population data for the distribution of these SNPs of NPC1L1 has lead to the identification of six nsSNPs (non-synonymous single nucleotide polymorphism). The in vitro analysis using the software MuPro and StructureSNP shows that nsSNP M510I (rs1468384), which involves A!iG base pair change leads to decrease in the stability of the protein. A reproducible and a cost-effective PCR-RFLP based assay was developed to screen for the SNP distribution amongst the North Western Indian population as a test case. This SNP has been studied in Caucasian, Asian and African American populations. Till date, no data is available on Indian population. The allele distribution in Indian Population differs significantly from that of other populations. Moreover on investigating the effect of this nsSNP on the plasma lipid levels in the general population we found a profound association of this nsSNP with higher ranges of plasma lipid levels.