Proteomic footprint of serum urate concentration and urate transporter ABCG2 dysfunctional polymorphism: a cross-sectional study
Authors' conclusion
To the best of our knowledge, this is the first study to report a proteomic signature of SU concentration. These findings suggest that SU-associated proteomic signatures vary according to ABCG2 genotypes, highlighting the genetic contribution to pathophysiological processes associated with SU concentration variation.
Study context
- Population
- Japanese individuals aged ≥50 years2,886 proteins analysed
- Participants
- 176 individuals
- Exposure
- Association of serum urate (SU) concentration with serum proteomic profiles, overall and by ABCG2 p.Q141K genotype
- p.Q141K minor allele carriersn = 91
- Wild-type homozygotesn = 85reference
- Outcome
- Association between SU concentration and serum proteins (Olink Explore 3072)
Methodological detailslinear regression adjusted for age, sex, renal function and insulin resistance, false discovery rate threshold of 5%
- Linear regression adjusted for age, sex, renal function and insulin resistance
- False discovery rate threshold of 5%
Main finding
As reported in the abstract
Proteins analysed
2886
Proteins significantly associated with SU concentration
63
Strongest association: uromodulin (adjusted p)
adjusted p=2.21×10-5
Observational data: associations, not effects.
Further findings
- SU-associated proteins by ABCG2 p.Q141K genotype (subgroups) — p.Q141K minor allele carriers
- 11 events
SU-associated proteins by ABCG2 p.Q141K genotype (subgroups)
- Wild-type homozygotes (n=85): no significant SU-associated proteins detected
- Gene set enrichment: xenobiotic metabolism in wild-types; additional inflammation- and disease-related gene sets in minor allele carriers
Tissue-specific enrichment of the 63 SU-associated proteins
- Significantly enriched in the liver, kidneys and duodenum
Original publication
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