Population heterogeneity in the genetic control of serum urate.

Scanning of the genome in Caucasian cohorts for genes that control serum urate levels have revealed eight confirmed associations. Knowledge of genetic control of serum urate in other populations can be extrapolated from the study of gout, a condition of extreme hyperuricemia; three urate transport genes (SLC2A9, ABCG2, and SLC17A1/NPT1) have been studied in diverse populations (Caucasian, Asian, and Polynesian). Between-population heterogeneity is evident in allele frequency and association with gout, notably within Polynesian populations, which are defined by a geographic region and shared ancestry but also characterized by migratory events that create bottlenecks and alter genetic structure in the founder populations. Despite the large genome-wide studies in Caucasians, only 5% of the variance in serum urate levels has been explained. A more complete picture will be revealed by very large meta-analyses of genome-wide association scans in Caucasian and in other populations with less genetic heterogeneity than Caucasians.