Evidence mapPaperPMID 41826282Full record

Trial reportThe pharmacogenomics journal2026

A potential association of SLC2A9 variant rs7442295 with uric acid at baseline and in interaction with iloperidone.

Sandra P Smieszek, Sean R Chadwick, Emily L Czeisler, Rosarelis Torres, Haimeng Bai, Changfu Xiao, Christos M Polymeropoulos, Gunther Birznieks, Mihael H Polymeropoulos

Abstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in The pharmacogenomics journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Sandra P Smieszek *Vanda Pharmaceuticals, Inc., Washington, DC, 20037, USA. Sandra.Smieszek@vandapharma.com.ORCID 0000-0002-8006-0454
Sean R Chadwick *Vanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.ORCID 0000-0003-2424-7983
Emily L CzeislerVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.
Rosarelis TorresVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.
Haimeng BaiVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.ORCID 0000-0003-2833-0813
Changfu XiaoVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.
Christos M PolymeropoulosVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.
Gunther BirznieksVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.
Mihael H PolymeropoulosVanda Pharmaceuticals, Inc., Washington, DC, 20037, USA.

Funding

Non-US Government Research Support type
6 · The paper itself

Abstract

Circulating levels of uric acid are influenced by a complex mix of intrinsic and environmental factors, including genetics, diet, and drugs. We analyzed levels of uric acid in a recent phase 3 clinical trial of patients with bipolar mania treated with 24 mg/day of the antipsychotic iloperidone or placebo. Initial results revealed that iloperidone treatment was associated with increases in uric acid from baseline (LS mean change (SE) of 27.2 (-4.93) μmol/L, compared with a change of 0.1 (-4.77) μmol/L for placebo group (LS mean difference (95% CI) = 27.1 (14.94, 39.20), p = <0.0001). Similar results were further observed in a previous phase 3 study of iloperidone treatment of schizophrenia. Pharmacogenetic analysis examining the urate transporter SLC2A9 revealed that iloperidone associated increases were linked to a genetic variant (rs7442295), correlating with both urate levels at baseline and in interaction with iloperidone vs placebo, and a pronounced increase of 35.9 μmol/L (0.67 mg/dL) was seen in iloperidone-treated patients homozygous for the for the rs7442295 (G) allele at the SLC2A9 gene, compared to a decrease of -16.5 (0.31 μmol/L in the corresponding GG placebo group (LS mean difference (95% CI) = 40.79 (14.61, 66.96, p = 0.0024). Further investigation suggested potentially clinically relevant sex differences associated with this variant. Specifically, male GG genotype patients exhibiting more frequent shifts from above the upper limit of normal for iloperidone-treated patients in comparison to female, AG/AA, and placebo groups. Overall, the mechanism of this iloperidone-induced increase in serum urate levels is likely due to decrease in clearance of urate through interaction with the SLC2A9 urate transporter protein. These results may hold clinical significance for patients treated with iloperidone.

Indexed as

Antipsychotic AgentsBipolar DisorderGlucose Transport Proteins, FacilitativeIsoxazolesPiperidinesPolymorphism, Single NucleotideUric AcidAdultFemaleHumansMaleSchizophreniaAntipsychotic AgentsGlucose Transport Proteins, FacilitativeiloperidoneIsoxazolesPiperidinesSLC2A9 protein, humanUric Acid

Identifiers

PMID41826282
PMCPMC12987721

What Socratic holds

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Registered trials

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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 Socratic graph.