Genetic polymorphisms in Na⁺⁺-taurocholate co-transporting polypeptide (NTCP) and ileal apical sodium-dependent bile acid transporter (ASBT) and ethnic comparisons of functional variants of NTCP among Asian populations

다국어 초록 (Multilingual Abstract)

<OL><LI><P>Genetic variants of Na<SUP>++</SUP>-taurocholate co-transporting polypeptide (NTCP; <I>SLC10A1</I>) and ileal apical sodium-dependent bile acid transporter (ASBT; <I>SLC10A2</I>), which greatly contribute to bile acid homeostasis, were extensively explored in the Korean population and functional variants of NTCP were compared among Asian populations.</P></LI><LI><P>From direct DNA sequencing, six SNPs were identified in the <I>SLC10A1</I> gene and 14 SNPs in the <I>SLC10A2</I> gene. Three of seven coding variants were non-synonymous SNPs: two variants from <I>SLC10A1</I> (A64T, S267F) and one from <I>SLC10A2</I> (A171S). No linkage was analysed in the <I>SLC10A1</I> gene because of low frequencies of genetic variants, and the <I>SLC10A2</I> gene was composed of two separated linkage disequilibrium blocks contrary to the white population.</P></LI><LI><P>The stably transfected NTCP-A64T variant showed significantly decreased uptakes of taurocholate and rosuvastatin compared with wild-type NTCP. The decreased taurocholate uptake and increased rosuvastatin uptake were shown in the NTCP-S267F variant. The allele frequencies of these functional variants were 1.0% and 3.1%, respectively, in a Korean population. However, NTCP-A64T was not found in Chinese and Vietnamese subjects. The frequency distribution of NTCP-S267F in Koreans was significantly lower than those in Chinese and Vietnamese populations.</P></LI><LI><P>Our data suggest that NTCP-A64T and -S267F variants cause substrate-dependent functional change <I>in vitro</I>, and show ethnic difference in their allelic frequencies among Asian populations although the clinical relevance of these variants is remained to be evaluated.</P></LI></OL>