title: 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.
abstract: Genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP; SLC10A1) and ileal apical sodium-dependent bile acid transporter (ASBT; SLC10A2), which greatly contribute to bile acid homeostasis, were extensively explored in the Korean population and functional variants of NTCP were compared among Asian populations. From direct DNA sequencing, six SNPs were identified in the SLC10A1 gene and 14 SNPs in the SLC10A2 gene. Three of seven coding variants were non-synonymous SNPs: two variants from SLC10A1 (A64T, S267F) and one from SLC10A2 (A171S). No linkage was analysed in the SLC10A1 gene because of low frequencies of genetic variants, and the SLC10A2 gene was composed of two separated linkage disequilibrium blocks contrary to the white population. 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. Our data suggest that NTCP-A64T and -S267F variants cause substrate-dependent functional change in vitro, and show ethnic difference in their allelic frequencies among Asian populations although the clinical relevance of these variants is remained to be evaluated.
authors.affiliation: Department of Pharmacology, Inje University College of Medicine, Jin-gu, Busan, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.forename: Im-Sook
authors.initials: IS
authors.lastname: Song
authors.forename: Ho-Jung
authors.initials: HJ
authors.lastname: Shin
authors.forename: Min-Hye
authors.initials: MH
authors.lastname: Kim
authors.forename: Yeong-Lim
authors.initials: YL
authors.lastname: Choi
authors.forename: Su-Jeong
authors.initials: SJ
authors.lastname: Lim
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Sang-Seop
authors.initials: SS
authors.lastname: Lee
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D044466:Asian People; D001646:Bile / Q000378:metabolism; D005464:Fluorobenzenes / Q000378:metabolism; D005787:Gene Frequency; D056914:Genomic Structural Variation; D006801:Humans; D015810:Linkage Disequilibrium; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism
chemical_list: D005464:Fluorobenzenes; D029363:Organic Anion Transporters, Sodium-Dependent; D011743:Pyrimidines; D013449:Sulfonamides; D027981:Symporters; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D000068718:Rosuvastatin Calcium