Novel Insights into the Effects of Genetic Variants on Serum Urate Response to an Acute Fructose Challenge: A Pilot Study

Overview

Journal Nutrients

Date 2022 Oct 14

PMID 36235682

Authors

Xinruo Zhang

Baba B Mass

Valentina Talevi

Ruixue Hou

Kari E North

Venkata Saroja Voruganti

Affiliations

Soon will be listed here.

Abstract

Studies have shown that genetic variations can influence metabolic response to nutrient intake, and that diets rich in fructose contribute to hyperuricemia. In this pilot study, our aim was to determine the variability of serum urate in response to an acute fructose challenge and to investigate if genetic variants would affect this response in young to middle-aged adults who self-reported as Black or White. Fifty-seven participants consumed a fructose-rich beverage after an overnight fast. Blood was drawn at five time points (baseline, 30, 60, 120, and 180 min after consumption). Thirty urate-related single nucleotide polymorphisms (SNPs) were analyzed for their associations with baseline serum urate and its percent changes, using a two-step modeling approach followed by meta-analysis. At baseline, serum urate (mg/dL, mean ± SD) was higher in Whites (5.60 ± 1.01 vs. 5.37 ± 0.96), men (6.17 ± 1.14 vs. 5.24 ± 0.79), and those with obesity (5.69 ± 1.08 vs. 5.42 ± 1.06 vs. 5.34 ± 0.80). Three SNPs were significantly associated with baseline serum urate or its percent changes, and six SNPs were nominally associated with percent changes in serum urate. In summary, our results showed that genetic variants could play a role in short-term urate metabolism.

References

Ravich W, Bayless T, Thomas M . Fructose: incomplete intestinal absorption in humans. Gastroenterology. 1983; 84(1):26-9. View

Dalbeth N, House M, Gamble G, Horne A, Pool B, Purvis L . Population-specific influence of SLC2A9 genotype on the acute hyperuricaemic response to a fructose load. Ann Rheum Dis. 2013; 72(11):1868-73. DOI: 10.1136/annrheumdis-2012-202732. View

Prestin K, Wolf S, Feldtmann R, Hussner J, Geissler I, Rimmbach C . Transcriptional regulation of urate transportosome member SLC2A9 by nuclear receptor HNF4α. Am J Physiol Renal Physiol. 2014; 307(9):F1041-51. DOI: 10.1152/ajprenal.00640.2013. View

Okegawa T, Ushio K, Imai M, Morimoto M, Hara T . Orphan nuclear receptor HNF4G promotes bladder cancer growth and invasion through the regulation of the hyaluronan synthase 2 gene. Oncogenesis. 2013; 2:e58. PMC: 3740288. DOI: 10.1038/oncsis.2013.25. View

Nath S, Saroja Voruganti V, Arar N, Thameem F, Lopez-Alvarenga J, Bauer R . Genome scan for determinants of serum uric acid variability. J Am Soc Nephrol. 2007; 18(12):3156-63. DOI: 10.1681/ASN.2007040426. View

Wang J, Zhang J, Xu L, Zheng Y, Ling D, Yang Z . Expression of HNF4G and its potential functions in lung cancer. Oncotarget. 2018; 9(26):18018-18028. PMC: 5915054. DOI: 10.18632/oncotarget.22933. View

Keenan R . The biology of urate. Semin Arthritis Rheum. 2020; 50(3S):S2-S10. DOI: 10.1016/j.semarthrit.2020.04.007. View

Borrell L, Elhawary J, Fuentes-Afflick E, Witonsky J, Bhakta N, Wu A . Race and Genetic Ancestry in Medicine - A Time for Reckoning with Racism. N Engl J Med. 2021; 384(5):474-480. PMC: 8979367. DOI: 10.1056/NEJMms2029562. View

Leask M, Dowdle A, Salvesen H, Topless R, Fadason T, Wei W . Functional Urate-Associated Genetic Variants Influence Expression of lincRNAs and . Front Genet. 2019; 9:733. PMC: 6348267. DOI: 10.3389/fgene.2018.00733. View

10.

Lanaspa M, Tapia E, Soto V, Sautin Y, Sanchez-Lozada L . Uric acid and fructose: potential biological mechanisms. Semin Nephrol. 2011; 31(5):426-32. DOI: 10.1016/j.semnephrol.2011.08.006. View

11.

Tin A, Li Y, Brody J, Nutile T, Chu A, Huffman J . Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels. Nat Commun. 2018; 9(1):4228. PMC: 6185909. DOI: 10.1038/s41467-018-06620-4. View

12.

Chen-Xu M, Yokose C, Rai S, Pillinger M, Choi H . Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007-2016. Arthritis Rheumatol. 2019; 71(6):991-999. PMC: 6536335. DOI: 10.1002/art.40807. View

13.

Tin A, Marten J, Kuhns V, Li Y, Wuttke M, Kirsten H . Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels. Nat Genet. 2019; 51(10):1459-1474. PMC: 6858555. DOI: 10.1038/s41588-019-0504-x. View

14.

Nakatochi M, Kanai M, Nakayama A, Hishida A, Kawamura Y, Ichihara S . Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals. Commun Biol. 2019; 2:115. PMC: 6453927. DOI: 10.1038/s42003-019-0339-0. View

15.

Caliceti C, Calabria D, Roda A, Cicero A . Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review. Nutrients. 2017; 9(4). PMC: 5409734. DOI: 10.3390/nu9040395. View

16.

Capuano V, Marchese F, Capuano R, Torre S, Iannone A, Capuano E . Hyperuricemia as an independent risk factor for major cardiovascular events: a 10-year cohort study from Southern Italy. J Cardiovasc Med (Hagerstown). 2017; 18(3):159-164. DOI: 10.2459/JCM.0000000000000347. View

17.

Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S . A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021; 53(10):1415-1424. DOI: 10.1038/s41588-021-00931-x. View

18.

Saroja Voruganti V, Laston S, Haack K, Mehta N, Cole S, Butte N . Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study. Am J Clin Nutr. 2015; 101(4):725-32. PMC: 4381775. DOI: 10.3945/ajcn.114.095364. View

19.

Stanhope K, Medici V, Bremer A, Lee V, Lam H, Nunez M . A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Am J Clin Nutr. 2015; 101(6):1144-54. PMC: 4441807. DOI: 10.3945/ajcn.114.100461. View

20.

Bruun J, Maersk M, Belza A, Astrup A, Richelsen B . Consumption of sucrose-sweetened soft drinks increases plasma levels of uric acid in overweight and obese subjects: a 6-month randomised controlled trial. Eur J Clin Nutr. 2015; 69(8):949-53. DOI: 10.1038/ejcn.2015.95. View