Hyperuricemia (HU), elevated levels of serum urate, is a prerequisite for gouty arthritis. The SLC2A9 gene that encodes a urate transporter tops the list of hyperuricemic genes . It is a key genetic determinant of serum uric acid (SUA) levels and explains about 3% of SUA variance .
Analysis of resequence data to identify and characterize variants within the SLC2A9 locus conferring susceptibility to hyperuricemia specifically in the New Zealand Māori and Pacific Islander (Polynesian) population.
The SLC2A9 locus was resequenced in approximately 800 individuals comprising hyperuricemic cases and normouricemic controls. Based on self-reported ancestry, the cohort was split into two subsets (Polynesian, n=440 and European, n=368). All Polynesians were from NZ while Europeans were from NZ and the United States. Association analysis was carried out to identify non-synonymous risk variants within the SLC2A9 locus that confer risk for HU. Multiply adjusted logistic regression analysis was carried out using R.
A total of 3964 variants were identified within the SLC2A9 locus. Over a hundred variants were found to be significant in the Polynesian population (OR=0.10[0.01;0.88]-5.43[1.93;15.33], POR=0.00028-0.049, MAFcontrols=0.014-0.535, MAFcases=0.002-0.546). Twenty five of these variants were found to be Polynesian-specific, eleven known and fourteen novel. These Polynesian-specific variants will be further analysed, annotated, and genotyped in a larger cohort as a continuation of this study.
These findings will aid in the identification of penetrant variants that could be applied in precision medicine and public health genomics.