Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout: biochemical, molecular genetics and functional analysis
Abstract
Gout is caused by hyperuricaemia. Several genes involved in renal urate transport, such as SLC2A9, ABCG2 and SLC22A12, have been identified as risk factors for hyperuricaemia and gout.
More recently, a genome-wide association study of gout uncovered that single-nucleotide polymorphisms (SNPs) of SLC2A9 and ABCG2 are associated with two types of gout, renal underexcretion and renal overload, respectively. The genome-wide association study, however, has limitations in establishing causality of disease-associated SNPs.
Therefore, experimental validations are essential to determine if interesting variants are indeed responsible for clinical symptoms. As reported in our previous study of common SLC2A9 allelic variants, we detected variants with no evidence of an association with hyperuricaemia and gout.
In this letter we present a biochemical, molecular genetic and functional case study suggesting a causal link between a hitherto undescribed sequence variant in the ABCG2 gene and a severe gouty phenotype.