title: Identification and functional analysis of variants in the human concentrative nucleoside transporter 2, hCNT2 (SLC28A2) in Chinese, Malays and Indians.
abstract: The human concentrative nucleoside transporter (hCNT2), also known as SLC28A2, plays an important role in the cellular uptake across intestinal membrane of some naturally occurring nucleosides and nucleoside analogs. This study aims to determine the genetic variability of hCNT2 (SLC28A2) in three major Asian ethnic groups residing in Singapore: Chinese, Malay and Indian, and functionally characterize the variants of hCNT2. Healthy participants (n=96) from each group were screened for genetic variations in the exons of hCNT2 (SLC28A2) using denaturing high performance liquid chromatography and sequencing analyses. A total of 23 polymorphisms were identified in the exonic and flanking intronic regions, and ethnic differences in single nucleotide polymorphism frequencies were evident. Five novel nonsynonymous variants (L12R, R142H, E172D, E385K, M612T) were constructed by mutagenesis and functionally characterized in U-251 cells. Expression of these variants in U-251 cells revealed that all except E385K can uptake various substrates of hCNT2: inosine, ribavirin and uridine.
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Clinical Research Centre, Singapore.
authors: Linghui
authors: L
authors: Li
authors: Cherine Meng Fong
authors: CM
authors: Tan
authors: Seok Hwee
authors: SH
authors: Koo
authors: Kok Ting
authors: KT
authors: Chong
authors: Edmund Jon Deoon
authors: EJ
authors: Lee
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002681:China / Q000208:ethnology; D017931:DNA Primers / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007194:India / Q000208:ethnology; D008296:Malaysia / Q000208:ethnology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012846:Singapore
chemical_list: D017931:DNA Primers; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins; C065171:cif nucleoside transporter