The renal urate transporter SLC17A1 locus: confirmation of association with gout

Abstract

IntroductionTwo major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets.MethodsFive variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian.ResultsAt rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype.ConclusionWe confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.

Twenty-eight loci that influence serum urate levels: analysis of association with gout

“…Of the controls, 376 of the Europeans, and all the Polynesians, were also determined not to have gout by the ACR criteria. Based on previous reports,4 7 the Polynesian sample set was subdivided into Eastern Polynesian (EP; Cook Island and NZ Ma¯ori) people of higher Polynesian ancestry (EP/N; 334 cases, 395 controls), Eastern Polynesian people of lower Polynesian ancestry (EP/Z; 157 cases, 313 controls), people of Western Polynesian (WP; Samoa, Tonga, Niue, Tuvalu and Tokelau) ancestry (368 cases, 315 controls), and people of mixed Eastern and Western Polynesian ancestry (EP/WP; 29 cases, 72 controls) 4. For the analysis presented in table 2 the WP, EP/N and EP/WP sample sets were grouped into a higher Polynesian ancestry sample set.…”

“…Association of genetic variants with gout was tested using STATA V.8.0 software by logistic regression with adjustment for age and sex. The Polynesian sample sets were additionally adjusted by a genetic estimate of Polynesian ancestry, determined as previously described 4. Sample sets were combined by an inverse-variance weighted fixed-effect method, using STATA V.8.0 software.…”

Mitochondrial genetic variation and gout in Māori and Pacific people living in Aotearoa New Zealand

“…It occurs at high frequency among Māori and Pacific (Polynesian) people,1 in part because of their inherently high serum urate levels 2. Additional to its higher frequency among Polynesians, the disease also has increased severity (eg, increased prevalence of tophi and incidence of flares) and its onset typically occurs at a younger age 3. Genetic variation in transporters controlling renal and gut excretion of uric acid has been found to contribute to gout risk among Polynesian populations 3–7.…”

Gout: an Asia‐Pacific update

“…6 The major gout-causing genes identified are SLC2A9 and ABCG2, the urate transport genes and SLC17A1, which encodes sodiumdependent phosphate transporter 1, a renal transporter of uric acid. 7 Gout often presents as severe monoarthritis of acute onset in lower limb joints such as the first metatarsophalangeal (MTP) joint or ankle. The arthritis may subside completely but often recurs.…”