Association of rare and common genetic variants in MOCOS with inadequate response to allopurinol
Authors' conclusion
We provide evidence for common and rare genetic variation in MOCOS associating with allopurinol response.
Study context
- Population
- Participants with gout from the LASSO study whose whole genome was sequenced; adherence by pill counts, and in a subgroup by plasma oxypurinol >20μmol/lsubgroup n = 303 with plasma oxypurinol
- Participants
- 563 participants
- Comparison
- Rare and common variants in urate transporter and allopurinol-to-oxypurinol metabolic genes, good vs inadequate allopurinol response
- Outcome
- 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
Methodological detailswhole genome sequencing, sequence kernel association test (SKAT), subset of the LASSO study
- Whole genome sequencing
- Sequence kernel association test (SKAT)
- Subset of the LASSO study
Main finding
As reported in the abstract
- Allopurinol-to-oxypurinol gene group: PSKAT-C = 0.019
- MOCOS: PSKAT-C = 0.011
Further findings
| Outcome | P value |
|---|---|
| Association with allopurinol response when adherence confirmed by plasma oxypurinolAllopurinol-to-oxypurinol gene group | PSKAT-C = 0.002 |
| Association with allopurinol response when adherence confirmed by plasma oxypurinolMOCOS | PSKAT-C < 0.001 |
Association with allopurinol response when adherence confirmed by plasma oxypurinol
- Evidence for genetic association was stronger
Original publication
Association of rare and common genetic variants in MOCOS with inadequate response to allopurinol. Rheumatology (Oxford). Published 13 August 2024. doi:10.
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