The incidence of hyperuricemia and gout in China has been increasing year by year, with the incidence of hyperuricemia rising from 10.10% in 1998 to 17.90% in 2008, while the incidence of gout rose from 0.34% in 1998 to 2.0% in 2008. At present, there are 120 million patients with hyperuricemia and about 17 million patients with gout in China. In addition to the increase in incidence and number of patients, the proportion of young people suffering from gout is also increasing, which has factors of dietary structure, lifestyle, and genetic factors. The younger the age of onset, the greater the likelihood that genetic factors are involved in the onset. The causes of elevated uric acid and gout attacks are threefold: 1) decreased excretion of uric acid; 2) increased production of uric acid; and 3) increased deposition of uric acid in the joints. Current research has found that genetic defects are involved in these three pathophysiological mechanisms. 1. Genes that reduce uric acid excretion (1) SLC22A12: this gene encodes a protein similar to the first two genes and also plays an important role in the excretion of uric acid from the kidney; (2) mutations in the SLC2A9 (encoding protein glucose transporter protein 9) gene: mainly expressed in the placenta and the proximal tubule of the kidney, if this gene is mutated, the activity of the encoded enzyme is reduced, which also leads to The mutation in this gene reduces the activity of the encoded enzyme and also leads to a reduction in blood uric acid excretion. Mutations in this gene are more likely to cause gout. (3) mutation of ABCG2 (adenosine triphosphate-binding transporter protein G superfamily) gene: the enzyme encoded by this gene is to assist in the excretion of blood uric acid from the kidney, once the mutation occurs, the ability of blood uric acid excretion from the kidney decreases, leading to an increase in blood uric acid. 2. Genes with increased uric acid production (1) MTHFR (methylenetetrahydrofolate reductase) mutation: The role of MTHFR is to metabolize and remove homocysteine. Homocysteine is a toxic amino acid that damages the cell wall of the endothelium. Homocysteine levels are increased when folate, B6 and/or B12 are deficient. When the MTHFR
C677T gene is mutated to TT (a pure mutation), it leads to insufficient folate production and a corresponding increase in homocysteine content, causing vascular endothelial damage, venous thrombosis, predisposing to cardiovascular and cerebrovascular diseases, and abnormally high blood uric acid. (2) Mutation of RGPRT (hypoxanthine guanine phosphate ribosyltransferase) gene: Mutation of this gene leads to a decrease in the activity of the key enzyme in the process of uric acid being reused in vivo, and uric acid cannot be used, resulting in an increase in blood uric acid. 3) Genes that contribute to the deposition of uric acid in joints. In addition, Chinese scholars have identified three novel gout susceptibility genes, BCAS3, RFX3, and KCNQ1, which may be involved in the pathological process of hyperuricemia progressing to gout through different mechanisms such as participation in inflammatory pathways and regulation of the immune system. The specific aspects involved need to be confirmed by further studies.