Gout and Its Risk Factors: A Review Based on Mendelian Randomization Analysis
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i1.3676
Abstract
Gout and its complications have caused an enormous health and economical burden worldwide. Understanding the underlying risk factors for gout and their causality as well as interactions can provide new insights into prevention and novel therapeutic strategies. Mendelian Randomization (MR) analysis is a research method that uses genetic variants as instruments to estimate the causal effect of a risk factor on an outcome, thereby reducing confounding in observational studies, the usage of such method along with the observational studies can provide valuable information and instruction to further pathophysiology studies and clinical practice. This narrative article aims to summarize the underlying risk factors and totalizing published MR analysis on gout. The systolic blood pressure, pulse pressure in cardiovascular system, body mass index, visceral adipose tissue, high-density lipoprotein, fast insulin in metabolism, tea, coffee in lifestyle, Victivallaceae family and the Ruminococcus gnavus and other 12 taxa of intestinal microbiota has been all proven to be casually associated with the development of gout, and other diseases/trait in these systems were associated with either serum uric acid level or hyperuricemia. Gout/serum uric acid level/hyperuricemia are as well had an impact on considerably diseases. These studies provide useful data and thoughtful insights to better assisting further studies in pathophysiology and clinical practice. Though several approaches have been developed to detect pleiotropy, more new method should be invented and practiced on MR analysis.
Keywords
Causality; Gout; Mendelian Randomization; Review; Risk factor; Hyperuricemia
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[2] S.-M. Dai, X.-H. Han, D.-B. Zhao,Y.-Q. Shi, Y. Liu, and J.-M. Meng, “Prevalence of Rheumatic Symptoms, Rheumatoid Arthritis, Ankylosing Spondylitis, and Gout in Shanghai, China: A COPCORD Study,” J. Rheumatol.
[3] Z. Miao et al., “Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China,” J. Rheumatol., vol. 35, no. 9, pp. 1859–1864, Sep. 2008.
[4] H. Nan et al., “The prevalence of hyperuricemia in a population of the coastal city of Qingdao, China,” J. Rheumatol., vol. 33, no. 7, pp. 1346–1350, Jul. 2006.
[5] J. Desai, S. Steiger, and H.-J. Anders, “Molecular Pathophysiology of Gout,” Trends Mol. Med., vol. 23, no. 8, pp. 756–768, Aug. 2017.
[6] N. Dalbeth, A. L. Gosling, A. Gaffo, and A. Abhishek, “Gout,” The Lancet, vol. 397, no. 10287, pp. 1843–1855, May 2021.
[7] B. L. Hainer, E. Matheson, andR. T. Wilkes, “Diagnosis, Treatment, and Prevention of Gout,” vol. 90, no. 12, 2014.
[8] E. Sandersonetal., “Mendelian randomization,” Nat. Rev. Methods Primer, vol. 2, no. 1, Art. no. 1, Feb. 2022.
[9] G. Sandoval-Plata, G. Nakafero, M. Chakravorty, K. Morgan, and A. Abhishek, “Association between serum urate, gout and comorbidities: a case–control study using data from the UK Biobank,” Rheumatology, vol. 60, no. 7, pp. 3243–3251, Jul. 2021, doi: 10.1093/rheumatology/keaa773.
[10] M. Kuwabara et al., “Asymptomatic Hyperuricemia Without Comorbidities Predicts Cardiometabolic Diseases: Five-Year Japanese Cohort Study,” Hypertension, vol. 69, no. 6, pp. 1036–1044, Jun. 2017.
[11] H. Tomiyama et al., “Involvement of Arterial Stiffness and Inflammation in Hyperuricemia-Related Development of Hypertension,” Hypertension, vol. 72, no. 3, pp. 739–745, Sep. 2018.
[12] Y. Yang et al., “The role of obesity, type 2 diabetes, and metabolic factors in gout: A Mendelian randomization study,” Front. Endocrinol., vol. 13, p. 917056, Aug. 2022.
[13] B. Laiet al., “Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures,” Arthritis Res. Ther., vol. 24, no. 1, p. 243, Oct. 2022.
[14] J. Zhu et al., “The Association of Hyperuricemia and Gout With the Risk of Cardiovascular Diseases: A Cohort and Mendelian Randomization Study in UK Biobank,” Front. Med., vol. 8, p. 817150, Mar. 2022.
[15] “Persistence of monosodium urate crystals and low‐grade inflammation in the synovial fluid of patients with untreated gout - Pascual - 1991 - Arthritis & Rheumatism - Wiley Online Library.” Accessed: Nov. 22, 2023. [Online].
[16] D. B. Corry, P. Eslami, K. Yamamoto, M. D. Nyby, H. Makino, and M. L. Tuck, “Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin–angiotensin system,” J. Hypertens., vol. 26, no. 2, p. 269, Feb. 2008.
[17] M. Kanbay et al., “Microvascular disease and its role in the brain and cardiovascular system: a potential role for uric acid as a cardiorenal toxin,” Nephrol. Dial. Transplant. Off. Publ. Eur. Dial. Transpl. Assoc. - Eur. Ren. Assoc., vol. 26, no. 2, pp. 430–437, Feb. 2011.
[18] S.-Y. Pan, R.-J. Cheng, Z.-J. Xia, Q.-P. Zhang, and Y. Liu, “Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies,” BMJ Open, vol. 11, no. 6, p. e041680, Jun. 2021.
[19] S. Lin, H. Zhang, and A. Ma, “Association of gout and depression: A systematic review and meta‐analysis,” Int. J. Geriatr. Psychiatry, vol. 33, no. 3, pp. 441–448, Mar. 2018.
[20] T. Liu et al., “A Meta-Analysis of Oxidative Stress Markers in Depression,” PLOS ONE, vol. 10, no. 10, p. e0138904, Oct. 2015.
[21] F. Bartoli, G. Trotta, C. Crocamo, M. R. Malerba, M. Clerici, and G. Carrà, “Antioxidant uric acid in treated and untreated subjects with major depressive disorder: a meta-analysis and meta-regression,” Eur. Arch. Psychiatry Clin. Neurosci., vol. 268, no. 2, pp. 119–127, Mar. 2018.
[22] S. S. Zhao, Y. Qian, S. L. Mackie, C. Wen, and Y. Mao, “Genetically predicted serum urate levels have no causal role on depression or other psychiatric disorders,” Clin. Rheumatol., vol. 40, no. 9, pp. 3729–3733, Sep. 2021.
[23] Y.-N. Ou et al., “The Association of Serum Uric Acid Level, Gout, and Alzheimer’s Disease: A Bidirectional Mendelian Randomization Study,” J. AlzheimersDis., vol. 89, no. 3, pp. 1063–1073, Jan. 2022.
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[26] R. Conget al., “Assessing the Causal Effects of Adipokines on Uric Acid and Gout: A Two-Sample Mendelian Randomization Study,” Nutrients, vol. 14, no. 5,p. 1091, Mar. 2022.
[27] S. C. Larsson, S. Burgess, and K. Michaëlsson, “Genetic association between adiposity and gout: a Mendelian randomization study,” Rheumatology, vol. 57, no. 12, pp. 2145–2148, Dec. 2018.
[28] “Obesity, hypertension and diuretic use as risk factors for incident gout: a systematic review and meta-analysis of cohort studies | Arthritis Research & Therapy | Full Text.” Accessed: Nov. 17, 2023. [Online].
[29] T. Karlsson, F. Hadizadeh, M. Rask-Andersen, Å. Johansson, and W. E. Ek, “Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses,” Arthritis Rheumatol., vol. 75, no. 11, pp. 2027–2035, 2023.
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[31] W. Xiao, Q. Wang, Y. Liu, H. Zhang, and H. Zou, “Association of visceral adipose tissue with gout: Observational and Mendelian randomization analyses,” Chin. Med. J. (Engl.), Oct. 2023.
[32] H. G. Choi et al., “Association between Gout and Dyslipidemia: A Nested Case– Control Study Using a National Health Screening Cohort,” J. Pers. Med., vol. 12, no. 4, p. 605, Apr. 2022.
[33] X. Yu, T. Wang, S. Huang, and P. Zeng, “Evaluation of the causal effects of blood lipid levels on gout with summary level GWAS data: two-sample Mendelian randomization and mediation analysis,” J. Hum. Genet., vol. 66,no. 5,pp. 465–473, May 2021.
[34] C. D. Adams and B. B. Boutwell, “Using multiple Mendelian randomization
approaches and genetic correlations to understand obesity, urate, and gout,” Sci. Rep., vol. 11, no. 1, p. 17799, Sep. 2021.
[35] Y. H. Lee, “Assessing the causal association between smoking behavior and risk of gout using a Mendelian randomization study,” Clin. Rheumatol., vol. 37, no. 11, pp. 3099–3105, Nov. 2018.
[36] T. Liu, Chinese tea: a cultural history and drinking guide. Beijing: China Intercontinental Press, 2010. Accessed: Nov. 23, 2023. [Online].
[37] X. Liang, J. Cai, and Y. Fan, “Causal association between tea intake and risk for gout: a Mendelian randomization study,” Front. Genet., vol. 14, p. 1220931, Jul. 2023.
[38] Y. Shirai et al., “Coffee Consumption Reduces Gout Risk Independently of Serum Uric Acid Levels: Mendelian Randomization Analyses Across Ancestry Populations,” ACR Open Rheumatol., vol. 4, no. 6, pp. 534–539, Jun. 2022.
[39] A. A. S. Syed et al., “The Relationship between Alcohol Consumption and Gout: A Mendelian Randomization Study,” Genes, vol. 13, no. 4, p. 557, Mar. 2022.
[40] X. Fang et al., “The Interaction Between Dietary Fructose and Gut Microbiota in Hyperuricemia and Gout,” Front. Nutr., vol. 9, p. 890730, Jun. 2022.
[41] J. Wei et al., “Association Between Gut Microbiota and Elevated Serum Urate in Two Independent Cohorts,” Arthritis Rheumatol., vol. 74, no. 4, pp. 682–691, 2022.
[42] Z. Wang et al., “Gut microbiota remodeling: A promising therapeutic strategy to confront hyperuricemia and gout,” Front. Cell. Infect. Microbiol., vol. 12, p. 935723, Aug. 2022.
[43] T. Hou et al., “Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization,” Front. Immunol., vol. 14, p. 1148591, Mar. 2023.
[44] M. Wang, J. Fan, Z. Huang, D. Zhou, and X. Wang, “Causal Relationship between Gut Microbiota and Gout: A Two-Sample Mendelian Randomization Study,” Nutrients, vol. 15, no. 19, p. 4260, Oct. 2023.
[45] R. K. Topless, A. Gaffo, L. K. Stamp, P. C. Robinson, N. Dalbeth, and T. R. Merriman, “Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study,” Lancet Rheumatol., vol. 4, no. 4, pp. e274–e281, Apr. 2022.
[46] N. Patel, J. L. Rein, L. Sanchez-Russo, J. Winston, and J. Uribarri, “COVID-19– Associated Acute Kidney Injury: A Case Series,” Kidney Med., vol. 2, no. 5, pp. 668–669, Sep. 2020.
[47] D. Xie et al., “Gout and Excess Risk of Severe SARS – COV ‐2 Infection Among Vaccinated Individuals: A General Population Study,” Arthritis Rheumatol., vol. 75, no. 1, pp. 122–132, Jan. 2023.
[48] H. Penget al., “Gout and susceptibility and severity of COVID-19: A bidirectional Mendelian randomization analysis,” J. Infect., vol. 85, no. 3, pp. e59–e61, Sep. 2022.
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