Uric Acid Concentration, Serum, Quantitative Trait Locus 5

For a phenotypic description of gout and a discussion of genetic heterogeneity of serum uric acid concentration quantitative trait loci, see UAQTL1 (138900).

Mapping

Sulem et al. (2011) tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. Sulem et al. (2011) identified a low-frequency missense variant (1580C-G; rs150414818) in the ALDH16A1 gene (613358) on chromosome 19q13 associated with gout (OR = 3.12, p = 1.5 x 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 standard deviation, p = 4.5 x 10(-21)). The 1580C-G change results in a proline-to-arginine substitution at position 527 (P527R) encoded by the 17-exon transcript. The authors confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. Sulem et al. (2011) also found a second variant, on chromosome 1, associated with gout (UAQTL6; 614747).