Are polymorphisms affecting serum urate, renal urate handling and alcohol intake associated with co-morbidities in gout cases? A case–control study using data from the UK Biobank

Sandoval-Plata, Gabriela; Morgan, Kevin; Abhishek, Abhishek

Abstract

Objective: To examine the association between common comorbidities, eGFR and loci involved in the hyperuricaemia-gout transition.

Methods: This study was conducted in people with gout from the UK Biobank. Logistic regression was used to examine the association between self-reported physician- diagnosed hypertension, diabetes, hypercholesterolemia and ischaemic heart disease (IHD) with the following variants: rs1260326(GCKR), rs16890979(SLC2A9), rs2231142(ABCG2), rs1229984(ADH1B) and rs2078267(SLC22A11) and adjusted for age, sex and 10-principal components. Linear regression was used to examine the association with eGFR.

Results: 7,049 participants with gout were included. After adjusting for multiple testing, there was a statistically significant positive association between urate lowering allele at SLC2A9 and hypertension, and negative association between urate raising allele at ABCG2 and hypertension (OR=1.17 and OR=0.86, respectively). Number of urate lowering risk alleles associated with hypertension (OR (95%CI) 1.13 (1.06-1.21)). High eGFR associated with urate raising allele at rs2231142 (β=1.38). The SNP in ADH1B that protects from alcohol excess showed a negative association with IHD (OR=0.53).

Conclusion: Unlike in general population studies urate lowering genetic variants associate with hypertension in gout patients with dose-response. This may be due to high prevalence of other risk factors of hypertension such as obesity, poor diet etc. and needs validation in independent datasets.

Citation

Sandoval-Plata, G., Morgan, K., & Abhishek, A. (2022). Are polymorphisms affecting serum urate, renal urate handling and alcohol intake associated with co-morbidities in gout cases? A case–control study using data from the UK Biobank. Rheumatology International, 42, 1617-1622. https://doi.org/10.1007/s00296-022-05148-7

• Journal Article Type: Article
• Acceptance Date: May 9, 2022
• Online Publication Date: May 28, 2022
• Publication Date: 2022-09
• Deposit Date: May 26, 2022
• Publicly Available Date: Jun 6, 2022
• Journal: Rheumatology International
• Print ISSN: 0172-8172
• Electronic ISSN: 1437-160X
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Pages: 1617-1622
• DOI: https://doi.org/10.1007/s00296-022-05148-7
• Keywords: Immunology; Immunology and Allergy; Rheumatology
• Public URL: https://nottingham-repository.worktribe.com/output/8224726
• Publisher URL: https://link.springer.com/article/10.1007/s00296-022-05148-7