| Title: | Associations between dietary micronutrient intake and serum urate concentrations are dependent on SLC2A9 polymorphism rs12498742: A UK Biobank cohort study |
| Journal: | Journal of Nutrition |
| Published: | 2 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42235823/ |
| DOI: | https://doi.org/10.1016/j.tjnut.2026.101627 |
Publication 19795
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Abstract
BACKGROUND: Serum urate (SU) concentrations are associated with increased risk of type 2 diabetes, metabolic syndrome, and gout. Both genetic and lifestyle factors can alter SU. The role of genetics in modifying associations between diet and SU is not well understood.</p>
OBJECTIVE: We examined if associations between dietary micronutrient intake and SU are modulated by genetic risk for high SU.</p>
METHODS: We utilized the UK Biobank, with 108,992 participants following exclusions. Micronutrient intake was measured by 24-hour recall. Polygenic risk scores (PRSs) were generated to estimate genetic risk. Single-nucleotide polymorphisms (SNPs) from 30 known urate-risk genes were examined to identify micronutrient-gene interaction loci. Custom PRSs designed to lack a single gene locus allowed for contrasting individual genes with remaining genetic risk. Micronutrient-gene interactions were analyzed for SU using linear regression with an interaction term. Results were deemed significant at false discovery rate (FDR) <0.05.</p>
RESULTS: Significant interactions were observed between overall genetic risk and niacin, pantothenic acid, vitamin B6, biotin, folate, magnesium, total iron, non-heme iron, zinc, manganese, copper, and iodine (FDR<0.05). Higher intakes of these micronutrients were associated with larger decreases in SU concentrations in subjects with higher genetic risk. These interactions were largely replicated with one SNP, SLC2A9 rs12498742. All interactions with the PRS, ceased after the SLC2A9 gene was removed, suggesting SLC2A9 as the primary locus of interaction. Analyses, stratified by the number of rs12498742 risk alleles, were indicative of effect modification for riboflavin, pantothenic acid, biotin, calcium, and magnesium and suggest that dietary intake of these micronutrients may be more impactful to those with higher genetic risk from SLC2A9 rs12498742.</p>
CONCLUSION: The urate-lowering potential of various micronutrients may be dependent on SLC2A9 rs12498742 genotype. Individuals with the highest genetic risk from SLC2A9 rs12498742 may benefit the most from dietary micronutrients associated with lower SU.</p>
11 Authors
- Parker R Johnson
- Parker A Huizinga
- Aiden Y Kim
- Cameron J Cardona
- Riju Sigdel
- Jillian M Joyce
- McKale R Montgomery
- Dingbo Lin
- Yoo Kim
- Sam R Emerson
- Winyoo Chowanadisai
1 Application
| Application ID | Title |
|---|---|
| 88625 | Role of micronutrient metabolism and genetics in health outcomes and biomarkers |
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