Evidence map›Paper›PMID 39137147›Full record

ArticleRheumatology (Oxford, England)2024

Association of rare and common genetic variants in MOCOS with inadequate response to allopurinol.

Niamh C Fanning, Murray Cadzow, Ruth K Topless, Chris Frampton, Nicola Dalbeth, Tony R Merriman, Lisa K Stamp

Abstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Hyperuricaemia and gout in the Pacific.Nature reviews. Rheumatology · 2025
    Review
  2. The genetics of gout: translation into clinical practice.Therapeutic advances in musculoskeletal disease · 2025
    Review
  3. Clinical and genetic analysis ofFrontiers in genetics · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Niamh C FanningDepartment of Medicine, University of Otago, Christchurch, Aotearoa, New Zealand.ORCID 0000-0003-4473-6063
Murray CadzowDepartment of Biochemistry, University of Otago, Dunedin, Aotearoa, New Zealand.ORCID 0000-0002-2299-4136
Ruth K ToplessDepartment of Biochemistry, University of Otago, Dunedin, Aotearoa, New Zealand.
Chris FramptonDepartment of Medicine, University of Otago, Christchurch, Aotearoa, New Zealand.
Nicola DalbethDepartment of Medicine, University of Auckland, Auckland, Aotearoa, New Zealand.ORCID 0000-0003-4632-4476
Tony R MerrimanDepartment of Biochemistry, University of Otago, Dunedin, Aotearoa, New Zealand.ORCID 0000-0003-0844-8726
Lisa K StampDepartment of Medicine, University of Otago, Christchurch, Aotearoa, New Zealand.ORCID 0000-0003-0138-2912

Funding

ArdeaBiosciencesAstraZenecaHealth Research Council of New Zealand 08/075Mateponapona Aotearoa R312
6 · The paper itself

Abstract

objectivesThe minor allele of the common rs2231142 ABCG2 variant predicts inadequate response to allopurinol urate lowering therapy. We hypothesize that additional variants in genes encoding urate transporters and allopurinol-to-oxypurinol metabolic enzymes also predict allopurinol response.

methodsThis study included a subset of participants with gout from the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO), whose whole genome was sequenced (n = 563). Good responders had a 4:1 or 5:1 ratio of good [serum urate (SU) <0.36 mmol/l on allopurinol ≤300 mg/day] to poor (SU ≥0.36 mmol/l despite allopurinol >300 mg/day) responses over five to six time points, while inadequate responders had a 1:4 or 1:5 ratio of good to poor responses. Adherence to allopurinol was determined by pill counts, and for a subgroup (n = 303), by plasma oxypurinol >20μmol/l. Using the sequence kernel association test (SKAT), we estimated the combined effect of rare and common variants in urate secretory (ABCC4, ABCC5, ABCG2, SLC17A1, SLC17A3, SLC22A6, SLC22A8) and reuptake genes (SLC2A9, SLC22A11) and in allopurinol-to-oxypurinol metabolic genes (AOX1, MOCOS, XDH) on allopurinol response.

resultsThere was an association of rare and common variants in the allopurinol-to-oxypurinol gene group (PSKAT-C = 0.019), and in MOCOS, encoding molybdenum cofactor sulfurase, with allopurinol response (PSKAT-C = 0.011). Evidence for genetic association with allopurinol response in the allopurinol-to-oxypurinol gene group (PSKAT-C = 0.002) and MOCOS (PSKAT-C < 0.001) was stronger when adherence to allopurinol therapy was confirmed by plasma oxypurinol.

conclusionWe provide evidence for common and rare genetic variation in MOCOS associating with allopurinol response.

Indexed as

AllopurinolATP Binding Cassette Transporter, Subfamily G, Member 2GoutGout SuppressantsAgedATP-Binding Cassette, Sub-Family C ProteinsFemaleGenetic VariationGlucose Transport Proteins, FacilitativeHumansMaleMedication AdherenceMiddle AgedNeoplasm ProteinsOxypurinolUric AcidABCC4 protein, humanABCG2 protein, humanAllopurinolATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily G, Member 2Glucose Transport Proteins, FacilitativeGout SuppressantsNeoplasm ProteinsOxypurinolSLC2A9 protein, humanUric Acidallopurinoldrug responsegeneticsgout

Identifiers

PMID39137147
PMCPMC11534095

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.