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原发性痛风易感基因研究现状
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Abstract:
痛风是一种严重影响健康和生活质量的代谢性疾病，受到遗传因素和环境因素共同作用，且近年来患病率呈上升趋势。原发性痛风是一种多基因遗传性疾病，其发病及临床特征具有明显的遗传特异性。近年来，随着分子生物学技术的发展，全基因组关联分析(Genome-wide association studies, GWAS)已经检测到了导致痛风的多个易感位点和相关候选基因。本文简要介绍了这些基因以及其基因突变位点在痛风发病机制中的作用和对痛风发病的影响，以及这些基因与环境危险因素之间的潜在相互作用，以促进人们对痛风发病机制的理解。
Gout is a metabolic disease that seriously affects health and quality of life. It is affected by both ge-netic and environmental factors, and its prevalence has been increasing in recent years. Primary gout is a polygenic genetic disease with significant genetic specificity in its pathogenesis and clinical characteristics. In recent years, with the development of molecular biology technology, ge-nome-wide association studies (GWAS) have detected multiple susceptibility sites and related can-didate genes that cause gout. This article briefly introduces the role of these genes and their muta-tion sites in the pathogenesis of gout and their impact on the pathogenesis of gout, as well as the potential interactions between these genes and environmental risk factors, in order to promote people’s understanding of the pathogenesis of gout.
| [1] | Sivera, F., andres, M. and Dalbeth, N. (2022) A Glance into the Future of Gout. Therapeutic Advances in Musculoskele-tal Disease, 14. https://doi.org/10.1177/1759720X221114098 |
| [2] | Dalbeth, N., Merriman, T.R. and Stamp, L.K. (2016) Gout. The Lancet, 388, 2039-2052.
https://doi.org/10.1016/S0140-6736(16)00346-9 |
| [3] | Campion, E.W., Glynn, R.J. and Delabry, L.O. (1987) Asymptomatic Hyperuricemia. Risks and Consequences in the Normative Aging Study. The American Journal of Medi-cine, 82, 421-426.
https://doi.org/10.1016/0002-9343(87)90441-4 |
| [4] | Zhang, W.-Z. (2021) Why Does Hyperuricemia Not Neces-sarily Induce Gout? Biomolecules, 11, Article No. 280.
https://doi.org/10.3390/biom11020280 |
| [5] | Dalbeth, N. and Stamp, L. (2014) Hyperuricaemia and Gout: Time for a New Staging System? Annals of Rheumatic Diseases, 73, 1598-1600. https://doi.org/10.1136/annrheumdis-2014-205304 |
| [6] | 唐莹莹, 成志锋. 原发性痛风与高尿酸血症相关基因的研究进展[J]. 医学综述, 2015, 21(19): 3483-3485. |
| [7] | Hediger, M.A., Johnson, R.J., Miyazaki, H., et al. (2005) Molecular Physiology of Urate Transport. Physiology (Bethesda), 20, 125-133. https://doi.org/10.1152/physiol.00039.2004 |
| [8] | 郑敏, 麻骏武. 高尿酸血症和痛风的遗传学研究进展[J]. 遗传, 2016, 38(4): 300-313. |
| [9] | Wilcox, W.R. and Khalaf, A.A. (1975) Nucleation of Monosodium Urate Crystals. An-nals of Rheumatic Diseases, 34, 332-339. https://doi.org/10.1136/ard.34.4.332 |
| [10] | Tak, H.K., Cooper, S.M. and Wilcox, W.R. (1980) Studies on the Nucleation of Monosodium Urate at 37？C. Arthritis & Rheumatology, 23, 574-580. https://doi.org/10.1002/art.1780230509 |
| [11] | Mcgill, N.W. and Dieppe, P.A. (1991) The Role of Serum and Syno-vial Fluid Components in the Promotion of Urate Crystal Formation. The Journal of Rheumatology, 18, 1042-1045. |
| [12] | Chhana, A., Lee, G. and Dalbeth, N. (2015) Factors Influencing the Crystallization of Monosodium Urate: A Systematic Literature Review. BMC Musculoskeletal Disorders, 16, Article No. 296.
https://doi.org/10.1186/s12891-015-0762-4 |
| [13] | Katz, W.A. and Schubert, M. (1970) The Interaction of Monoso-dium Urate with Connective Tissue Components. Journal of Clinical Investigation, 49, 1783-1789. https://doi.org/10.1172/JCI106396 |
| [14] | Narang, R.K. and Dalbeth, N. (2020) Pathophysiology of Gout. Seminars in Nephrology, 40, 550-563.
https://doi.org/10.1016/j.semnephrol.2020.12.001 |
| [15] | Kippen, I., Klinenberg, J.R., Weinberger, A., et al. (1974) Factors Affecting Urate Solubility in Vitro. Annals of Rheumatic Diseases, 33, 313-317. https://doi.org/10.1136/ard.33.4.313 |
| [16] | Paik, S., Kim, J.K., Silwal, P., et al. (2021) An Update on the Regulatory Mechanisms of NLRP3 Inflammasome Activation. Cellular & Molecular Immunology, 18, 1141-1160. https://doi.org/10.1038/s41423-021-00670-3 |
| [17] | Zhao, J., Wei, K., Jiang, P., et al. (2022) Inflammatory Response to Regulated Cell Death in Gout and Its Functional Implications. Frontiers in Immunology, 13, Article ID: 888306. https://doi.org/10.3389/fimmu.2022.888306 |
| [18] | Bauernfeind, F.G., Horvath, G., Stutz, A., et al. (2009) Cutting Edge: NF-kappaB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression. The Journal of Immunology, 183, 787-791. https://doi.org/10.4049/jimmunol.0901363 |
| [19] | Dalbeth, N., Gosling, A.L., Gaffo, A., et al. (2021) Gout. The Lancet, 397, 1843-1855.
https://doi.org/10.1016/S0140-6736(21)00569-9 |
| [20] | Sriranganathan, M.K., Vinik, O., Pardo, J., et al. (2021) In-terventions for Tophi in Gout. Cochrane Database of Systematic Reviews, 8, CD010069. https://doi.org/10.1002/14651858.CD010069.pub3 |
| [21] | Kuo, C.-F., Grainge, M.J., Zhang, W., et al. (2015) Global Epidemiology of Gout: Prevalence, Incidence and Risk Factors. Nature Reviews Rheumatology, 11, 649-662. https://doi.org/10.1038/nrrheum.2015.91 |
| [22] | K？ttgen, A., Albrecht, E., Teumer, A., et al. (2013) Genome-Wide Association Analyses Identify 18 New Loci Associated with Serum Urate Concentrations. Nature Genetics, 45, 145-154. https://doi.org/10.1038/ng.2500 |
| [23] | 白雪, 邱洪斌, 王景涛, 等. 原发性痛风和高尿酸血症相关基因研究现状[J]. 海南医学院学报, 2019, 25(16): 1275-1280. |
| [24] | Merriman, T.R. (2015) An Update on the Genetic Architecture of Hyperuricemia and Gout. Arthritis Research & Therapy, 17, Article No. 98. https://doi.org/10.1186/s13075-015-0609-2 |
| [25] | Klück, V., Liu, R. and Joosten, L.A.B. (2021) The Role of Inter-leukin-1 Family Members in Hyperuricemia and Gout. Joint Bone Spine, 88, Article ID: 105092. https://doi.org/10.1016/j.jbspin.2020.105092 |
| [26] | 张蓓. 尿酸转运及白介素基因与不同民族高尿酸血症及肾功能的差异研究[D]: [博士学位论文]. 乌鲁木齐: 新疆医科大学, 2015. |
| [27] | Nian, Y.-L. and You, C.-G. (2022) Sus-ceptibility Genes of Hyperuricemia and Gout. Hereditas, 159, Article No. 30.
https://doi.org/10.1186/s41065-022-00243-y |
| [28] | Woodward, O.M., K？ttgen, A., Coresh, J., et al. (2009) Identifi-cation of a Urate Transporter, ABCG2, with a Common Functional Polymorphism Causing Gout. Proceedings of the Na-tional Academy of Sciences of the United States of America, 106, 10338-10342. https://doi.org/10.1073/pnas.0901249106 |
| [29] | Eckenstaler, R. and Benndorf, R.A. (2021) The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update. International Journal of Molecular Sciences, 22, Ar-ticle No. 6678.
https://doi.org/10.3390/ijms22136678 |
| [30] | Matsuo, H., Takada, T., Nakayama, A., et al. (2014) ABCG2 Dysfunc-tion Increases the Risk of Renal Overload Hyperuricemia. Nucleosides, Nucleotides & Nucleic Acids, 33, 266-274.
https://doi.org/10.1080/15257770.2013.866679 |
| [31] | Chen, C.-J., Tseng, C.-C., Yen, J.-H., et al. (2018) ABCG2 Contributes to the Development of Gout and Hyperuricemia in a Genome-Wide Association Study. Scientific Reports, 8, Article No. 3137.
https://doi.org/10.1038/s41598-018-21425-7 |
| [32] | 吴蕾, 何耀, 张迪. ABCG2基因rs2231142位点基因多态性与东亚人群痛风相关性研究的Meta分析[J]. 中华流行病学杂志, 2015, 36(11): 1291-1296. |
| [33] | Kim, Y.S., Kim, Y., Park, G., et al. (2015) Genetic Analysis of ABCG2 and SLC2A9 Gene Polymorphisms in Gouty Arthritis in a Ko-rean Population. The Korean Journal of Internal Medicine, 30, 913-920.
https://doi.org/10.3904/kjim.2015.30.6.913 |
| [34] | Tu, H.-P., Chung, C.-M., Min-Shan Ko, A., et al. (2016) Additive Composite ABCG2, SLC2A9 and SLC22A12 Scores of High-Risk Alleles with Alcohol Use Modulate Gout Risk. Journal of Human Genetics, 61, 803-810.
https://doi.org/10.1038/jhg.2016.57 |
| [35] | Lee, Y.H., Seo, Y.H., Kim, J.H., et al. (2017) Associations between SLC2A9 Polymorphisms and Gout Susceptibility: A Meta-Analysis. Zeitschrift für Rheumatologie, 76, 64-70. https://doi.org/10.1007/s00393-016-0070-x |
| [36] | Meng, Q., Yue, J., Shang, M., et al. (2015) Correlation of GLUT9 Polymorphisms with Gout Risk. Medicine (Baltimore), 94, e1742. https://doi.org/10.1097/MD.0000000000001742 |
| [37] | Hollis-Moffatt, J.E., Xu, X., Dalbeth, N., et al. (2009) Role of the Urate Transporter SLC2A9 Gene in Susceptibility to Gout in New Zealand Māori, Pacific Island, and Caucasian Case-Control Sample Sets. Arthritis & Rheumatology, 60, 3485-3492. https://doi.org/10.1002/art.24938 |
| [38] | 游玉权. SLC2A9、SLC17A3、ABCG2基因单核苷酸多态性与痛风易感性的研究[D]: [硕士学位论文]. 福州: 福建医科大学, 2013. |
| [39] | Robinson, P.C., Taylor, W.J. and Dalbeth, N. (2015) An Observational Study of Gout Prevalence and Quality of Care in a National Australian General Practice Population. The Journal of Rheumatology, 42, 1702-1707.
https://doi.org/10.3899/jrheum.150310 |
| [40] | Kolz, M., Johnson, T., Sanna, S., et al. (2009) Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations. PLOS Genetics, 5, e1000504. |
| [41] | Anzai, N., Enomoto, A. and Endou, H. (2005) Renal Urate Handling: Clinical Relevance of Recent Advances. Current Rheumatology Reports, 7, 227-234. https://doi.org/10.1007/s11926-996-0044-0 |
| [42] | Hagos, Y., Stein, D., Ugele, B., et al. (2007) Human Renal Or-ganic Anion Transporter 4 Operates as an Asymmetric Urate Transporter. Journal of the American Society of Nephrology, 18, 430-439.
https://doi.org/10.1681/ASN.2006040415 |
| [43] | Ichida, K. (2009) What Lies behind Serum Urate Concentration? Insights from Genetic and Genomic Studies. Genome Medicine, 1, Article No. 118. https://doi.org/10.1186/gm118 |
| [44] | Enomoto, A., Kimura, H., Chairoungdua, A., et al. (2002) Molecular Identifi-cation of a Renal Urate Anion Exchanger That Regulates Blood Urate Levels. Nature, 417, 447-452. https://doi.org/10.1038/nature742 |
| [45] | Yang, Q., K？ttgen, A., Dehghan, A., et al. (2010) Multiple Genetic Loci In-fluence Serum Urate Levels and Their Relationship with Gout and Cardiovascular Disease Risk Factors. Circulation: Cardiovascular Genetics, 3, 523-530.
https://doi.org/10.1161/CIRCGENETICS.109.934455 |
| [46] | Tin, A., Woodward, O.M., Kao, W.H.L., et al. (2011) Genome-Wide Association Study for Serum Urate Concentrations and Gout among African Americans Identifies Ge-nomic Risk Loci and a Novel URAT1 Loss-of-Function Allele. Human Molecular Genetics, 20, 4056-4068. https://doi.org/10.1093/hmg/ddr307 |
| [47] | Choi, H.K., Atkinson, K., Karlson, E.W., et al. (2004) Purine-Rich Foods, Dairy and Protein Intake, and the Risk of Gout in Men. The New England Journal of Medicine, 350, 1093-1103. https://doi.org/10.1056/NEJMoa035700 |
| [48] | Beyl, R.N., Hughes, L. and Morgan, S. (2016) Update on Importance of Diet in Gout. The American Journal of Medicine, 129, 1153-1158. https://doi.org/10.1016/j.amjmed.2016.06.040 |
| [49] | Choi, H.K., Atkinson, K., Karlson, E.W., et al. (2004) Alcohol Intake and Risk of Incident Gout in Men: A Prospective Study. The Lancet, 363, 1277-1281. https://doi.org/10.1016/S0140-6736(04)16000-5 |
| [50] | Helget, L.N. and Mikuls, T.R. (2022) Environmental Trig-gers of Hyperuricemia and Gout. Rheumatic Disease Clinics of North America, 48, 891-906. https://doi.org/10.1016/j.rdc.2022.06.009 |
| [51] | Choi, H.K. and Curhan, G. (2008) Soft Drinks, Fructose Consump-tion, and the Risk of Gout in Men: Prospective Cohort Study. BMJ, 336, 309-312. https://doi.org/10.1136/bmj.39449.819271.BE |
| [52] | Ryu, H.J., Seo, M.R., Choi, H.J., et al. (2021) Particulate Mat-ter (PM10) as a Newly Identified Environmental Risk Factor for Acute Gout Flares: A Time-Series Study. Joint Bone Spine, 88, Article ID: 105108.
https://doi.org/10.1016/j.jbspin.2020.105108 |
| [53] | Tang, Y.-X., Bloom, M.S., Qian, Z.M., et al. (2021) Association between Ambient Air Pollution and Hyperuricemia in Traffic Police Officers in China: A Cohort Study. International Journal of Environmental Health Research, 31, 54-62.
https://doi.org/10.1080/09603123.2019.1628926 |
| [54] | Wang, H.-H., Zhang, S.-C., Wang, J., et al. (2020) Com-bined Toxicity of Outdoor Air Pollution on Kidney Function among Adult Women in Mianyang City, Southwest China. Chemosphere, 238, Article ID: 124603.
https://doi.org/10.1016/j.chemosphere.2019.124603 |
| [55] | He, Y.-S., Wang, G.-H., Wu, Z.-D., et al. (2022) Associ-ation between Non-Optimal Temperature and Hospitalizations for Gout in Anqing, China: A Time-Series Analysis. En-vironmental Science and Pollution Research International, 29, 13797-13804. https://doi.org/10.1007/s11356-021-16580-w |
| [56] | Wu, Z.-D., Yang, X.-K., He, Y.-S., et al. (2022) Environmental Factors and Risk of Gout. Environmental Research, 212, Article ID: 113377. https://doi.org/10.1016/j.envres.2022.113377 |
| [57] | 马丽岩, 成志锋. 痛风的遗传基础[J]. 医学综述, 2016, 22(4): 646-649. |
| [58] | Kuo, C.-F., Grainge, M.J., See, L.-C., et al. (2015) Familial Aggregation of Gout and Relative Genetic and Environmental Contributions: A Nationwide Population Study in Taiwan. Annals of Rheumatic Diseases, 74, 369-374.
https://doi.org/10.1136/annrheumdis-2013-204067 |
| [59] | Prior, I.A., Welby, T.J., Ostbye, T., et al. (1987) Migration and Gout: The Tokelau Island Migrant Study. British Medical Journal (Clinical Research Ed.), 295, 457-461. https://doi.org/10.1136/bmj.295.6596.457 |
| [60] | Danve, A., Sehra, S.T. and Neogi, T. (2021) Role of Diet in Hype-ruricemia and Gout. Best Practice & Research: Clinical Rheumatology, 35, Article ID: 101723. https://doi.org/10.1016/j.berh.2021.101723 |
| [61] | Nieradko-Iwanicka, B. (2022) The Role of Alcohol Consumption in Pathogenesis of Gout. Critical Reviews in Food Science and Nutrition, 62, 7129-7137. https://doi.org/10.1080/10408398.2021.1911928 |
| [62] | Choi, H.K. and Curhan, G. (2004) Beer, Liquor, and Wine Consumption and Serum Uric Acid Level: The Third National Health and Nutrition Examination Survey. Arthritis & Rheumatology, 51, 1023-1029.
https://doi.org/10.1002/art.20821 |
| [63] | Hamajima, N., Naito, M., Okada, R., et al. (2012) Significant Interaction between LRP2 rs2544390 in Intron 1 and Alcohol Drinking for Serum Uric Acid Levels among a Japanese Population. Gene, 503, 131-136.
https://doi.org/10.1016/j.gene.2012.04.064 |
| [64] | Kamatani, Y., Matsuda, K., Okada, Y., et al. (2010) Genome-Wide Association Study of Hematological and Biochemical Traits in a Japanese Population. Nature Genetics, 42, 210-215. https://doi.org/10.1038/ng.531 |
| [65] | Yamanaka, H., Kamatani, N., Hakoda, M., et al. (1994) Analysis of the Geno-types for Aldehyde Dehydrogenase 2 in Japanese Patients with Primary Gout. Advances in Experimental Medicine and Biology, 370, 53-56.
https://doi.org/10.1007/978-1-4615-2584-4_13 |
| [66] | Shibuya, A. and Yoshida, A. (1988) Frequency of the Atypi-cal Aldehyde Dehydrogenase-2 Gene (ALDH2(2)) in Japanese and Caucasians. The American Journal of Human Ge-netics, 43, 741-743. |
| [67] | Shibuya, A. and Yoshida, A. (1988) Genotypes of Alcohol-Metabolizing Enzymes in Japanese with Alcohol Liver Diseases: A Strong Association of the Usual Caucasian-Type Aldehyde Dehydrogenase Gene (ALDH1(2)) with the Disease. The American Journal of Human Genetics, 43, 744-748. |
| [68] | Stirpe, F., Della Corte, E., Bonetti, E., et al. (1970) Fructose-Induced Hyperuricaemia. The Lancet, 2, 1310-1311.
https://doi.org/10.1016/S0140-6736(70)92269-5 |
| [69] | Dalbeth, N., House, M.E., Gamble, G.D., et al. (2013) Pop-ulation-Specific Influence of SLC2A9 Genotype on the Acute Hyperuricaemic Response to a Fructose Load. Annals of Rheumatic Diseases, 72, 1868-1873.
https://doi.org/10.1136/annrheumdis-2012-202732 |
