[Functional analysis of +11G > A single nucleotide polymorphisms in intron 3 of human urate transporter 1 gene].

Objective: We reported previously that single nucleotide polymorphisms (SNP) +11G >A in intron 3 of the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese. The aim of the present study was to evaluate the effect of the variants on hURAT1 function.

Methods: The wild-type, mutant-type hURAT1 and exon 5-null hURAT1 were constructed, and respectively microinjected into the zebrafish embryo yolks. The subcellular localization of different genotypes of hURAT1 was detected by confocal laser scanning microscope.

Results: Compared with wild type, the mutant recombinant plasmid transcribed two types of mRNA spliceosome, the wild type and the exon 5-null type. The hURAT1 wild type protein was prominent localized on cell membrane, while the mutant type and exon 5-null hURAT1 proteins were distributed uniform in the cytoplasm but not on the cell membrane.

Conclusion: The hURAT1 variant +11G>A resulted in an alternative splicing of hURAT1 mRNA- exon 5-null type. Its protein product exhibited a different subcellular localization compared with that of wild type.