Objective There is no evidence for genetic association of the organic anion transporters (OAT) 1-3 (SLC22A6, SLC22A7, SLC22A8) and multi-drug resistance protein 4 (MRP4; ABCC4) with serum urate or gout. The Māori and Pacific (Polynesian) population of New Zealand (NZ) has the highest prevalence of gout worldwide. Our aim was to determine if there were any Polynesian population-specific genetic variants in the SLC22A6-8 and ABCC4 genes associated with gout. Participants and Methods All participants had ≥3 self-reported Māori and/or Pacific grandparents. From the total sample set of 1808 participants, 191 hyperuricaemic and 202 normouricaemic individuals were resequenced over the four genes with the remaining 1415 individuals used for replication. Regression analyses were performed adjusting by age, sex and Polynesian ancestry. To study the functional effect of non-synonymous variants ABCC4 transport assays were done in Xenopus laevis ooctyes. Results A total of 39 common variants were detected, with an ABCC4 variant (rs4148500) significantly associated with hyperuricemia and gout. Rs4148500 was monomorphic (for the protective major allele) in Europeans. There was evidence for association for rs4148500 with gout in the resequenced samples (OR=1.62, P=0.012) that was replicated (OR=1.25, P=0.033) and restricted to males (ORMales =1.43, P=0.001; ORFemales =0.98, P=0.89). The gout risk allele was associated with FEUA in males (β=-0.570, P=0.01). A rare population-specific variant (P1036L) with strong functional consequence reduced the uric acid transport activity of ABCC4 by 30%. Conclusion Association of ABCC4 with gout and FEUA is consistent with the established role of MRP4 as a unidirectional renal uric acid efflux pump. This article is protected by copyright. All rights reserved.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Chemistry
1
3%
Other
0
0%
Unknown
14
39%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 27. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 June 2017.
All research outputs
#1,523,469
of 26,847,662 outputs
Outputs from Arthritis & Rheumatology
#497
of 3,156 outputs
Outputs of similar age
#27,895
of 336,222 outputs
Outputs of similar age from Arthritis & Rheumatology
#13
of 68 outputs
Altmetric has tracked 26,847,662 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,156 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.2. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 336,222 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
