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Drug Metab Pharmacokinet. 2009;24(2):161-6.

Identification of functional promoter haplotypes of human concentrative nucleoside transporter 2, hCNT2 (SLC28A2).

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  • 1Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract

The human concentrative nucleoside transporter 2 (hCNT2) plays a major role in the intestinal absorption of naturally occurring nucleosides as well as some nucleoside analog drugs. To determine if single nucleotide polymorphisms (SNPs) in the promoter region of hCNT2 affect gene expression, we examined approximately 1 kb upstream the hCNT2 transcription start site. Ninety Chinese samples were screened and seven SNPs were identified: -115T>G, -146T>A, -264A>G, -564G>A, -861A>C, -880T>C and -906C>T. Based on these seven variants and their relative positions, eight haplotypes were identified using PHASE v2.1.1. Three naturally occurring haplotypes were cloned into the pGL3-Basic vector and transfected into HEK293 cells. Dual luciferase assay revealed that haplotype 4 (GTAGACC) and 7 (GAGAACT) exhibited significantly lower expression levels compared to the published haplotype 1 (TTAGATC). Results from our in-vitro study showed that the hCNT2 promoter region haplotype may modulate gene expression and cause different drug responses.

PMID:
19430172
[PubMed - indexed for MEDLINE]
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