Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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A combination of red and processed meat intake and polygenic risk score influences the incidence of hyperuricemia in middle-aged Korean adults

  • Suyeon Lee (Department of Food and Nutrition, Inha University) ;
  • Dayeon Shin (Department of Food and Nutrition, Inha University)
  • Received : 2024.06.06
  • Accepted : 2024.08.22
  • Published : 2024.10.01
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Abstract

BACKGROUND/OBJECTIVES: The high consumption of purine-rich meat is associated with hyperuricemia. However, there is limited evidence linking the consumption of red and processed meat to the genetic risk of hyperuricemia. We investigated the relationship between various combinations of red and processed meat consumption and the polygenic risk scores (PRSs) and the incidence of hyperuricemia in middle-aged Koreans. SUBJECTS/METHODS: We analyzed the data from 44,053 participants aged ≥40 years sourced from the Health Examinees (HEXA) cohort of the Korean Genome and Epidemiology Study (KoGES). Information regarding red and processed meat intake was obtained using a semiquantitative food frequency questionnaire (SQ-FFQ). We identified 69 independent single-nucleotide polymorphisms (SNPs) at uric acid-related loci using genome-wide association studies (GWASs) and clumping analyses. The individual PRS, which is the weighted sum of the effect size of each allele at the SNP, was calculated. We used multivariable Cox proportional hazards models adjusted for covariates to determine the relationship between red and processed meat intake and the PRS in the incidence of hyperuricemia. RESULTS: During an average follow-up period of 5 years, 2,556 patients with hyperuricemia were identified. For both men and women, the group with the highest red and processed meat intake and the highest PRS was positively associated with the development of hyperuricemia when compared with the group with the lowest red and processed meat intake and the lowest PRS (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.10-3.53; P < 0.0001; HR, 3.28; 95% CI, 2.45-4.40; P < 0.0001). CONCLUSION: Individuals at a high genetic risk for uric acid levels should moderate their consumption of red and processed meat to prevent hyperuricemia.

Keywords

Acknowledgement

This study was conducted using bioresources from the National Biobank of Korea, the Korea Disease Control and Prevention Agency (KDCA), Republic of Korea (KBN-2020-016).

References

  1. Neogi T. Clinical practice. Gout. N Engl J Med 2011;364:443-52.
  2. Li L, Yang C, Zhao Y, Zeng X, Liu F, Fu P. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: a systematic review and meta-analysis based on observational cohort studies. BMC Nephrol 2014;15:122.
  3. Kuwabara M, Niwa K, Nishi Y, Mizuno A, Asano T, Masuda K, Komatsu I, Yamazoe M, Takahashi O, Hisatome I. Relationship between serum uric acid levels and hypertension among Japanese individuals not treated for hyperuricemia and hypertension. Hypertens Res 2014;37:785-9.
  4. Dehghan A, van Hoek M, Sijbrands EJ, Hofman A, Witteman JC. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care 2008;31:361-2.
  5. Zheng L, Zhu Y, Ma Y, Zhang H, Zhao H, Zhang Y, Yang Z, Liu Y. Relationship between hyperuricemia and the risk of cardiovascular events and chronic kidney disease in both the general population and hypertensive patients: a systematic review and meta-analysis. Int J Cardiol 2024;399:131779.
  6. Chen JH, Chuang SY, Chen HJ, Yeh WT, Pan WH. Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum 2009;61:225-32.
  7. Trifiro G, Morabito P, Cavagna L, Ferrajolo C, Pecchioli S, Simonetti M, Bianchini E, Medea G, Cricelli C, Caputi AP, et al. Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann Rheum Dis 2013;72:694-700.
  8. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum 2011;63:3136-41.
  9. Esche J, Krupp D, Mensink GB, Remer T. Dietary potential renal acid load is positively associated with serum uric acid and odds of hyperuricemia in the German adult population. J Nutr 2018;148:49-55.
  10. Singh G, Lingala B, Mithal A. Gout and hyperuricaemia in the USA: prevalence and trends. Rheumatology (Oxford) 2019;58:2177-80.
  11. Ting K, Gill TK, Keen H, Tucker GR, Hill CL. Prevalence and associations of gout and hyperuricaemia: results from an Australian population-based study. Intern Med J 2016;46:566-73.
  12. Zhang M, Zhu X, Wu J, Huang Z, Zhao Z, Zhang X, Xue Y, Wan W, Li C, Zhang W, et al. Prevalence of hyperuricemia among Chinese adults: findings from two nationally representative cross-sectional surveys in 2015-16 and 2018-19. Front Immunol 2022;12:791983.
  13. Jeong H, Chang YS, Jeon CH. Association between hyperuricemia and hearing impairment: results from the Korean National Health and Nutrition Examination Survey. Medicina (Kaunas) 2023;59:1273.
  14. Lee CH, Sung NY. The prevalence and features of Korean gout patients using the National Health Insurance Corporation database. J Rheum Dis 2011;18:94-100.
  15. Kim JW, Kwak SG, Lee H, Kim SK, Choe JY, Park SH. Prevalence and incidence of gout in Korea: data from the national health claims database 2007-2015. Rheumatol Int 2017;37:1499-506.
  16. Williams PT. Effects of diet, physical activity and performance, and body weight on incident gout in ostensibly healthy, vigorously active men. Am J Clin Nutr 2008;87:1480-7.
  17. Kaneko K, Aoyagi Y, Fukuuchi T, Inazawa K, Yamaoka N. Total purine and purine base content of common foodstuffs for facilitating nutritional therapy for gout and hyperuricemia. Biol Pharm Bull 2014;37:709-21.
  18. Choi HK, Liu S, Curhan G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2005;52:283-9.
  19. Emmerson BT. The management of gout. N Engl J Med 1996;334:445-51.
  20. Schmidt JA, Crowe FL, Appleby PN, Key TJ, Travis RC. Serum uric acid concentrations in meat eaters, fish eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort. PLoS One 2013;8:e56339.
  21. Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z, Chen X, Xu F, Wang F, Sun R, et al. Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol 2008;35:1859-64.
  22. Cho SK, Kim S, Chung JY, Jee SH. Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1. BMJ Open 2015;5:e009360.
  23. Jang WC, Nam YH, Park SM, Ahn YC, Park SH, Choe JY, Shin IH, Kim SK. T6092C polymorphism of SLC22A12 gene is associated with serum uric acid concentrations in Korean male subjects. Clin Chim Acta 2008;398:140-4.
  24. Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, Mangino M, Albrecht E, Wallace C, Farrall M, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet 2009;5:e1000504.
  25. Woodward OM, Kottgen A, Coresh J, Boerwinkle E, Guggino WB, Kottgen M. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci U S A 2009;106:10338-42.
  26. Kottgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, Pistis G, Ruggiero D, O'Seaghdha CM, Haller T, et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 2013;45:145-54.
  27. Tin A, Marten J, Halperin Kuhns VL, Li Y, Wuttke M, Kirsten H, Sieber KB, Qiu C, Gorski M, Yu Z, et al. Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels. Nat Genet 2019;51:1459-74.
  28. Martin AR, Kanai M, Kamatani Y, Okada Y, Neale BM, Daly MJ. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet 2019;51:584-91.
  29. Lambert SA, Abraham G, Inouye M. Towards clinical utility of polygenic risk scores. Hum Mol Genet 2019;28:R133-42.
  30. Nakatochi M, Kanai M, Nakayama A, Hishida A, Kawamura Y, Ichihara S, Akiyama M, Ikezaki H, Furusyo N, Shimizu S, et al. Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals. Commun Biol 2019;2:115.
  31. Lewis CM, Vassos E. Polygenic risk scores: from research tools to clinical instruments. Genome Med 2020;12:44.
  32. Choi SW, Mak TS, O'Reilly PF. Tutorial: a guide to performing polygenic risk score analyses. Nat Protoc 2020;15:2759-72.
  33. Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, Natarajan P, Lander ES, Lubitz SA, Ellinor PT, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 2018;50:1219-24.
  34. Mavaddat N, Michailidou K, Dennis J, Lush M, Fachal L, Lee A, Tyrer JP, Chen TH, Wang Q, Bolla MK, et al. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes. Am J Hum Genet 2019;104:21-34.
  35. Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, Adams MJ, Agerbo E, Air TM, Andlauer TMF, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet 2018;50:668-81.
  36. Janssens AC. Validity of polygenic risk scores: are we measuring what we think we are? Hum Mol Genet 2019;28:R143-50.
  37. Kim Y, Han BG; KoGES group. Cohort profile: the Korean Genome and Epidemiology Study (KoGES) consortium. Int J Epidemiol 2017;46:e20.
  38. Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kimm K, Park C, Kim DH. Validation and reproducibility of food frequency questionnaire for Korean Genome Epidemiologic Study. Eur J Clin Nutr 2007;61:1435-41.
  39. Lee KW, Woo HD, Cho MJ, Park JK, Kim SS. Identification of dietary patterns associated with incidence of hyperglycemia in middle-aged and older Korean adults. Nutrients 2019;11:1801.
  40. Jeong J, Lim K, Shin S. The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: a prospective cohort study. Nutr Metab Cardiovasc Dis 2023;33:1158-66.
  41. Korea Disease Control and Prevention Agency. Korean Genome and Epidemiology Study. Manual of Korean Genome and Epidemiology Study-Food Frequency Questionnaire [Internet]. Cheongju: Korea Disease Control and Prevention Agency; 2019 [cited 2024 July 24]. Available from: https://nih.go.kr/ko/main/contents.do?menuNo=300583.
  42. Shin D, Lee KW. Dietary acid load is positively associated with the incidence of hyperuricemia in middleaged and older Korean adults: findings from the Korean Genome and epidemiology study. Int J Environ Res Public Health 2021;18:10260.
  43. Moon S, Kim YJ, Han S, Hwang MY, Shin DM, Park MY, Lu Y, Yoon K, Jang HM, Kim YK, et al. The Korea Biobank Array: design and identification of coding variants associated with blood biochemical traits. Sci Rep 2019;9:1382.
  44. Ko B, Jin HS. MACROD2 polymorphisms are associated with hypertension in Korean population. Korean J Clin Lab Sci 2019;51:57-63.
  45. Park HJ, Kim SS, Jin HS. Genetic polymorphisms of SLC8A1 are associated with hypertension and left ventricular hypertrophy in the Korean population. Korean J Clin Lab Sci 2019;51:286-93.
  46. Wu Y, Byrne EM, Zheng Z, Kemper KE, Yengo L, Mallett AJ, Yang J, Visscher PM, Wray NR. Genomewide association study of medication-use and associated disease in the UK Biobank. Nat Commun 2019;10:1891.
  47. Kim HR, Jin HS, Eom YB. Association between MANBA gene variants and chronic kidney disease in a Korean population. J Clin Med 2021;10:2255.
  48. Tyrrell J, Wood AR, Ames RM, Yaghootkar H, Beaumont RN, Jones SE, Tuke MA, Ruth KS, Freathy RM, Davey Smith G, et al. Gene-obesogenic environment interactions in the UK Biobank study. Int J Epidemiol 2017;46:559-75.
  49. Lee WJ, Lim JE, Jung HU, Kang JO, Park T, Won S, Rhee SY, Kim MK, Kim YJ, Oh B. Analysis of the interaction between polygenic risk score and calorie intake in obesity in the Korean population. Lifestyle Genom 2021;14:20-9.
  50. Lin KC, Lin HY, Chou P. Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen. J Rheumatol 2000;27:1045-50.
  51. Byun SH, Yoo DM, Lee JW, Choi HG. Analyzing the association between hyperuricemia and periodontitis: a cross-sectional study using KoGES HEXA data. Int J Environ Res Public Health 2020;17:4777.
  52. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, Streit J, Joseph-Ridge N. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005;353:2450-61.
  53. Nagahama K, Inoue T, Iseki K, Touma T, Kinjo K, Ohya Y, Takishita S. Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertens Res 2004;27:835-41.
  54. Lee KW, Shin D. Concurrent presence of high serum uric acid and inflammation is associated with increased incidence of type 2 diabetes mellitus in Korean adult population. Sci Rep 2022;12:11000.
  55. Fu J, Shin S. The association of dietary patterns with incident chronic kidney disease and kidney function decline among middle-aged Korean adults: a cohort study. Epidemiol Health 2023;45:e2023037.
  56. Moon ME, Jung DH, Heo SJ, Park B, Lee YJ. Oxidative balance score and new-onset type 2 diabetes mellitus in Korean adults without non-alcoholic fatty liver disease: Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort. Antioxidants 2024;13:107.
  57. Azadbakht L, Esmaillzadeh A. Red meat intake is associated with metabolic syndrome and the plasma C-reactive protein concentration in women. J Nutr 2009;139:335-9.
  58. Lee SA, Kwon SO, Song M, Choi JY, Shin A, Shu XO, Zheng W, Lee JK, Kang D. The association of serum high-sensitivity C-reactive protein level with the risk of site-specific cancer mortality: the Health Examinees (HEXA) study cohort. Am J Epidemiol 2022;191:2002-13.
  59. Cho GJ, Kim J, Kim JY, Han SW, Lee SB, Oh MJ, Kim SJ, Shin JE. Adverse pregnancy outcomes and maternal chronic diseases in the future: a cross-sectional study using KoGES-HEXA data. J Clin Med 2022;11:1457.
  60. Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol 2016;213:8-14.
  61. Mandal AK, Mount DB. The molecular physiology of uric acid homeostasis. Annu Rev Physiol 2015;77:323-45.
  62. Rivera-Paredez B, Macias-Kauffer L, Fernandez-Lopez JC, Villalobos-Comparan M, Martinez-Aguilar MM, de la Cruz-Montoya A, Ramirez-Salazar EG, Villamil-Ramirez H, Quiterio M, Ramirez-Palacios P, et al. Influence of genetic and non-genetic risk factors for serum uric acid levels and hyperuricemia in Mexicans. Nutrients 2019;11:1336.
  63. Abreu E, Fonseca MJ, Santos AC. Association between hyperuricemia and insulin resistance. Acta Med Port 2011;24 Suppl 2:565-74.
  64. Rule AD, de Andrade M, Matsumoto M, Mosley TH, Kardia S, Turner ST. Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families. Rheumatology (Oxford) 2011;50:871-8.
  65. Brandstatter A, Kiechl S, Kollerits B, Hunt SC, Heid IM, Coassin S, Willeit J, Adams TD, Illig T, Hopkins PN, et al. Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes Care 2008;31:1662-7.
  66. So A, Thorens B. Uric acid transport and disease. J Clin Invest 2010;120:1791-9.
  67. Dehghan A, Kottgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, Boerwinkle E, Levy D, Hofman A, Astor BC, et al. Association of three genetic loci with uric acid concentration and risk of gout: a genomewide association study. Lancet 2008;372:1953-61.
  68. Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, Ahmadi K, Dobson RJ, Marcano AC, Hajat C, et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet 2008;82:139-49.
  69. Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, Knott SA, Kolcic I, Polasek O, Graessler J, et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet 2008;40:437-42.
  70. Doring A, Gieger C, Mehta D, Gohlke H, Prokisch H, Coassin S, Fischer G, Henke K, Klopp N, Kronenberg F, et al. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet 2008;40:430-6.
  71. McArdle PF, Parsa A, Chang YP, Weir MR, O'Connell JR, Mitchell BD, Shuldiner AR. Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish. Arthritis Rheum 2008;58:2874-81.
  72. Guan M, Zhou D, Ma W, Chen Y, Zhang J, Zou H. Association of an intronic SNP of SLC2A9 gene with serum uric acid levels in the Chinese male Han population by high-resolution melting method. Clin Rheumatol 2011;30:29-35.
  73. Lyngdoh T, Bochud M, Glaus J, Castelao E, Waeber G, Vollenweider P, Preisig M. Associations of serum uric acid and SLC2A9 variant with depressive and anxiety disorders: a population-based study. PLoS One 2013;8:e76336.
  74. Sun X, Jiang F, Zhang R, Tang SS, Chen M, Peng DF, Yan J, Wang T, Wang SY, Bao YQ, et al. Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population. Acta Pharmacol Sin 2014;35:1421-7.
  75. Hu X, Rong S, Wang Q, Sun T, Bao W, Chen L, Liu L. Association between plasma uric acid and insulin resistance in type 2 diabetes: a Mendelian randomization analysis. Diabetes Res Clin Pract 2021;171:108542.
  76. Sun X, Zhang R, Jiang F, Tang S, Chen M, Peng D, Yan J, Wang T, Wang S, Bao Y, et al. Common variants related to serum uric acid concentrations are associated with glucose metabolism and insulin secretion in a Chinese population. PLoS One 2015;10:e0116714.
  77. Zhao J, Guo S, Schrodi SJ, He D. Trends in the contribution of genetic susceptibility loci to hyperuricemia and gout and associated novel mechanisms. Front Cell Dev Biol 2022;10:937855.
  78. Wong K, Briddon SJ, Holliday ND, Kerr ID. Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques. Biochim Biophys Acta 2016;1863:19-29.
  79. Li R, Miao L, Qin L, Xiang Y, Zhang X, Peng H, Mailamuguli , Sun Y, Yao H. A meta-analysis of the associations between the Q141K and Q126X ABCG2 gene variants and gout risk. Int J Clin Exp Pathol 2015;8:9812-23.
  80. Yu KH, Chang PY, Chang SC, Wu-Chou YH, Wu LA, Chen DP, Lo FS, Lu JJ. A comprehensive analysis of the association of common variants of ABCG2 with gout. Sci Rep 2017;7:9988.
  81. Lee S, Yang HK, Lee HJ, Park DJ, Kong SH, Park SK. Cross-phenotype association analysis of gastric cancer: in-silico functional annotation based on the disease-gene network. Gastric Cancer 2023;26:517-27.
  82. Wang J, Liu S, Wang B, Miao Z, Han L, Chu N, Zhang K, Meng D, Li C, Ma X. Association between gout and polymorphisms in GCKR in male Han Chinese. Hum Genet 2012;131:1261-5.
  83. Urano W, Taniguchi A, Inoue E, Sekita C, Ichikawa N, Koseki Y, Kamatani N, Yamanaka H. Effect of genetic polymorphisms on development of gout. J Rheumatol 2013;40:1374-8.
  84. Wang L, Ma Q, Yao H, He LJ, Fang BB, Cai W, Zhang B, Wang ZQ, Su YX, Du GL, et al. Association of GCKR rs780094 polymorphism with circulating lipid levels in type 2 diabetes and hyperuricemia in Uygur Chinese. Int J Clin Exp Pathol 2018;11:4684-94.
  85. Ho LJ, Lu CH, Su RY, Lin FH, Su SC, Kuo FC, Chu NF, Hung YJ, Liu JS, Hsieh CH. Association between glucokinase regulator gene polymorphisms and serum uric acid levels in Taiwanese adolescents. Sci Rep 2022;12:5519.
  86. Rasheed H, Stamp LK, Dalbeth N, Merriman TR. Interaction of the GCKR and A1CF loci with alcohol consumption to influence the risk of gout. Arthritis Res Ther 2017;19:161.
  87. Christensen EI, Birn H. Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol 2002;3:256-66.
  88. Kamatani Y, Matsuda K, Okada Y, Kubo M, Hosono N, Daigo Y, Nakamura Y, Kamatani N. Genomewide association study of hematological and biochemical traits in a Japanese population. Nat Genet 2010;42:210-5.
  89. Kanai M, Akiyama M, Takahashi A, Matoba N, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, et al. Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases. Nat Genet 2018;50:390-400.
  90. Rasheed H, Phipps-Green A, Topless R, Hollis-Moffatt JE, Hindmarsh JH, Franklin C, Dalbeth N, Jones PB, White DH, Stamp LK, et al. Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption. Arthritis Res Ther 2013;15:R177.
  91. Lan B, Chen P, Jiri M, He N, Feng T, Liu K, Jin T, Kang L. WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients. Rheumatol Int 2016;36:405-12.
  92. Cervero P, Himmel M, Kruger M, Linder S. Proteomic analysis of podosome fractions from macrophages reveals similarities to spreading initiation centres. Eur J Cell Biol 2012;91:908-22.
  93. Kile BT, Panopoulos AD, Stirzaker RA, Hacking DF, Tahtamouni LH, Willson TA, Mielke LA, Henley KJ, Zhang JG, Wicks IP, et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia. Blood 2007;110:2371-80.
  94. Wu JN, Koretzky GA. The SLP-76 family of adapter proteins. Semin Immunol 2004;16:379-93.
  95. Yu J, Riou C, Davidson D, Minhas R, Robson JD, Julius M, Arnold R, Kiefer F, Veillette A. Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1. Mol Cell Biol 2001;21:6102-12.
  96. Yang Q, Kottgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, Chasman DI, Aspelund T, Eiriksdottir G, Harris TB, et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet 2010;3:523-30.
  97. Hong M, Park JW, Yang PS, Hwang I, Kim TH, Yu HT, Uhm JS, Joung B, Lee MH, Jee SH, et al. A Mendelian randomization analysis: the causal association between serum uric acid and atrial fibrillation. Eur J Clin Invest 2020;50:e13300.
  98. Chiba T, Matsuo H, Kawamura Y, Nagamori S, Nishiyama T, Wei L, Nakayama A, Nakamura T, Sakiyama M, Takada T, et al. NPT1/SLC17A1 is a renal urate exporter in humans and its common gain-of-function variant decreases the risk of renal underexcretion gout. Arthritis Rheumatol 2015;67:281-7.
  99. Torres RJ, de Miguel E, Bailen R, Banegas JR, Puig JG. Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. J Rheumatol 2014;41:1863-70.
  100. Park JS, Kim Y, Kang J. Genome-wide meta-analysis revealed several genetic loci associated with serum uric acid levels in Korean population: an analysis of Korea Biobank data. J Hum Genet 2022;67:231-7.
  101. Dong Z, Zhou J, Jiang S, Li Y, Zhao D, Yang C, Ma Y, Wang Y, He H, Ji H, et al. Effects of multiple genetic loci on the pathogenesis from serum urate to gout. Sci Rep 2017;7:43614.
  102. Chen BD, Chen XC, Pan S, Yang YN, He CH, Liu F, Ma X, Gai MT, Ma YT. TT genotype of rs2941484 in the human HNF4G gene is associated with hyperuricemia in Chinese Han men. Oncotarget 2017;8:26918-26.
  103. Wisely GB, Miller AB, Davis RG, Thornquest AD Jr, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, et al. Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Structure 2002;10:1225-34.
  104. Kawaguchi M, Nakayama A, Aoyagi Y, Nakamura T, Shimizu S, Kawamura Y, Takao M, Tamura T, Hishida A, Nagayoshi M, et al. Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population. Hum Cell 2021;34:293-9.
  105. Leask MP, Merriman TR. The genetic basis of urate control and gout: insights into molecular pathogenesis from follow-up study of genome-wide association study loci. Best Pract Res Clin Rheumatol 2021;35:101721.
  106. Gottier Nwafor J, Nowik M, Anzai N, Endou H, Wagner CA. Metabolic acidosis alters expression of Slc22 transporters in mouse kidney. Kidney Blood Press Res 2020;45:263-74.
  107. Jamshidi N, Nigam KB, Nigam SK. Loss of the kidney urate transporter, Urat1, leads to disrupted redox homeostasis in mice. Antioxidants 2023;12:780.
  108. Sugihara S, Hisatome I, Kuwabara M, Niwa K, Maharani N, Kato M, Ogino K, Hamada T, Ninomiya H, Higashi Y, et al. Depletion of uric acid due to SLC22A12 (URAT1) loss-of-function mutation causes endothelial dysfunction in hypouricemia. Circ J 2015;79:1125-32.
  109. Shima Y, Teruya K, Ohta H. Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese. Life Sci 2006;79:2234-7.
  110. Matsuo H, Yamamoto K, Nakaoka H, Nakayama A, Sakiyama M, Chiba T, Takahashi A, Nakamura T, Nakashima H, Takada Y, et al. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes. Ann Rheum Dis 2016;75:652-9.
  111. Yang Y, Lin C, Zheng Q, Zhang L, Li Y, Huang Q, Wu T, Zhao Z, Li L, Luo J, et al. L-carnitine attenuated hyperuricemia-associated left ventricular remodeling through ameliorating cardiomyocytic lipid deposition. Front Pharmacol 2023;14:1016633.
  112. Cuevas-Delgado P, Miguel V, Ruperez FJ, Lamas S, Barbas C. Impact of renal tubular Cpt1a overexpression on the kidney metabolome in the folic acid-induced fibrosis mouse model. Front Mol Biosci 2023;10:1161036.
  113. Estiverne C, Mandal AK, Mount DB. Molecular pathophysiology of uric acid homeostasis. Semin Nephrol 2020;40:535-49.
  114. Narang RK, Vincent Z, Phipps-Green A, Stamp LK, Merriman TR, Dalbeth N. Population-specific factors associated with fractional excretion of uric acid. Arthritis Res Ther 2019;21:234.
  115. Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther 2015;17:98.
  116. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A 1981;78:6858-62.
  117. Leask M, Dowdle A, Salvesen H, Topless R, Fadason T, Wei W, Schierding W, Marsman J, Antony J, O'Sullivan JM, et al. Functional urate-associated genetic variants influence expression of lincRNAs LINC01229 and MAFTRR. Front Genet 2019;9:733.
  118. Merriman T, Phipps-Green A, Topless R, Merriman M, Franklin C, Jones G, van Rij A, Montgomery G, Chapman B, White D, et al. Association analysis of 18 recently discovered serum urate loci with gout. Ann Rheum Dis 2014;73:353.
  119. Phipps-Green AJ, Merriman ME, Topless R, Altaf S, Montgomery GW, Franklin C, Jones GT, van Rij AM, White D, Stamp LK, et al. Twenty-eight loci that influence serum urate levels: analysis of association with gout. Ann Rheum Dis 2016;75:124-30.
  120. Li C, Li Z, Liu S, Wang C, Han L, Cui L, Zhou J, Zou H, Liu Z, Chen J, et al. Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese. Nat Commun 2015;6:7041.
  121. Sakiyama M, Matsuo H, Nakaoka H, Kawamura Y, Kawaguchi M, Higashino T, Nakayama A, Akashi A, Ueyama J, Kondo T, et al. Common variant of BCAS3 is associated with gout risk in Japanese population: the first replication study after gout GWAS in Han Chinese. BMC Med Genet 2018;19:96.
  122. Lourida I, Hannon E, Littlejohns TJ, Langa KM, Hypponen E, Kuzma E, Llewellyn DJ. Association of lifestyle and genetic risk with incidence of dementia. JAMA 2019;322:430-7.
  123. Rutten-Jacobs LC, Larsson SC, Malik R, Rannikmae K, ; MEGASTROKE Consortium; International Stroke Genetics Consortium, Sudlow CL, Dichgans M, Markus HS, Traylor M. Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants. BMJ 2018;363:k4168.
  124. Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, et al. A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease. Nat Med 2023;29:1793-803.
  125. Said MA, Verweij N, van der Harst P. Associations of combined genetic and lifestyle risks with incident cardiovascular disease and diabetes in the UK Biobank study. JAMA Cardiol 2018;3:693-702.
  126. Arthur RS, Wang T, Xue X, Kamensky V, Rohan TE. Genetic factors, adherence to healthy lifestyle behavior, and risk of invasive breast cancer among women in the UK Biobank. J Natl Cancer Inst 2020;112:893-901.
  127. Xin J, Du M, Gu D, Jiang K, Wang M, Jin M, Hu Y, Ben S, Chen S, Shao W, et al. Risk assessment for colorectal cancer via polygenic risk score and lifestyle exposure: a large-scale association study of East Asian and European populations. Genome Med 2023;15:4.
  128. Zhang T, Gu Y, Meng G, Zhang Q, Liu L, Wu H, Zhang S, Wang X, Zhang J, Sun S, et al. Genetic risk, adherence to a healthy lifestyle, and hyperuricemia: the TCLSIH cohort study. Am J Med 2023;136:476-483.e5.
  129. Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women--the Third National Health and Nutrition Examination Survey. Arthritis Res Ther 2008;10:R116.
  130. Xiong Z, Zhu C, Qian X, Zhu J, Wu Z, Chen L. Serum uric acid is associated with dietary and lifestyle factors in elderly women in suburban Guangzhou in Guangdong province of south China. J Nutr Health Aging 2013;17:30-4.
  131. Li R, Yu K, Li C. Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review. Asia Pac J Clin Nutr 2018;27:1344-56.
  132. Zhang T, Gan S, Ye M, Meng G, Zhang Q, Liu L, Wu H, Gu Y, Zhang S, Wang Y, et al. Association between consumption of ultra-processed foods and hyperuricemia: TCLSIH prospective cohort study. Nutr Metab Cardiovasc Dis 2021;31:1993-2003.
  133. Rai SK, Fung TT, Lu N, Keller SF, Curhan GC, Choi HK. The Dietary Approaches to Stop Hypertension (DASH) diet, Western diet, and risk of gout in men: prospective cohort study. BMJ 2017;357:j1794.
  134. Zhang M, Chang H, Gao Y, Wang X, Xu W, Liu D, Li G, Huang G. Major dietary patterns and risk of asymptomatic hyperuricemia in Chinese adults. J Nutr Sci Vitaminol (Tokyo) 2012;58:339-45.
  135. Xia Y, Xiang Q, Gu Y, Jia S, Zhang Q, Liu L, Meng G, Wu H, Bao X, Yu B, et al. A dietary pattern rich in animal organ, seafood and processed meat products is associated with newly diagnosed hyperuricaemia in Chinese adults: a propensity score-matched case-control study. Br J Nutr 2018;119:1177-84.
  136. Lin K, McCormick N, Yokose C, Joshi AD, Lu N, Curhan GC, Merriman TR, Saag KG, Ridker PM, Buring JE, et al. Interactions between genetic risk and diet influencing risk of incident female gout: discovery and replication analysis of four prospective cohorts. Arthritis Rheumatol 2023;75:1028-38.
  137. Roman YM. Moving the needle in gout management: the role of culture, diet, genetics, and personalized patient are practices. Nutrients 2022;14:3590.