ASSOCIATION OF SOD2 (ALA16VAL), GPX4 (C718T), AND COL1A1 (C1997A) GENE POLYMORPHISMS WITH GOUTY NEPHROPATHY IN PATIENTS WITH GOUT

Gouty nephropathy is one of the most important renal complications of gout. Oxidative stress, chronic inflammation, and extracellular matrix remodeling play an important role in its development. Therefore, candidate genes involved in antioxidant defense and connective tissue metabolism may influence susceptibility to renal involvement in patients with gout. To evaluate the association of SOD2 (Ala16Val), GPX4 (C718T), and COL1A1 (C1997A) gene polymorphisms with gouty nephropathy in patients with gout. A case-control study included 186 individuals. The control group consisted of 96 healthy subjects. Ninety patients with gout were divided into two groups: Group 1 included 45 patients with gout without gouty nephropathy, and Group 2 included 45 patients with gouty nephropathy. Allelic and genotypic frequencies of SOD2 (Ala16Val), GPX4 (C718T), and COL1A1 (C1997A) polymorphisms were compared between the clinical groups and the control group. Statistical analysis included χ² test, odds ratio (OR), and p values. The strongest associations were observed for the SOD2 Ala16Val polymorphism in patients with gouty nephropathy. In Group 2, the Ala allele showed a protective association (χ²=8.81; p=0.003; OR=0.34), whereas the Val allele was associated with increased risk (χ²=8.81; p=0.003; OR=2.95). The Ala/Ala genotype also demonstrated a protective effect (χ²=5.26; p=0.022; OR=0.38), while the Val/Val genotype was associated with a markedly increased risk of nephropathy (χ²=5.52; p=0.019; OR=9.27). For GPX4 C718T, significant differences in Group 2 were found for the C allele (χ²=4.00; p=0.045; OR=0.60) and T allele (χ²=4.00; p=0.045; OR=1.67), while genotype-level associations were not statistically significant. For COL1A1 C1997A, Group 2 showed a lower frequency of the C allele (χ²=8.81; p=0.003; OR=0.34), a higher frequency of the A allele (χ²=8.81; p=0.003; OR=2.95), a protective effect of the C/C genotype (χ²=5.26; p=0.022; OR=0.38), and a significant association of the A/A genotype with nephropathy risk (χ²=5.52; p=0.019; OR=9.27). The results indicate that SOD2 (Ala16Val), GPX4 (C718T), and COL1A1 (C1997A) polymorphisms are associated with susceptibility to gouty nephropathy in patients with gout, with the strongest association observed for SOD2 Ala16Val. These findings support the potential role of molecular genetic markers in identifying gout patients at increased risk of renal involvement.痛风性肾病（Gouty nephropathy）是痛风最为重要的肾脏并发症之一。氧化应激、慢性炎症与细胞外基质重塑在其发病进程中发挥关键作用。因此，参与抗氧化防御及结缔组织代谢的候选基因，可能会影响痛风患者发生肾脏受累的易感性。 本研究旨在评估SOD2（Ala16Val）、GPX4（C718T）及COL1A1（C1997A）基因多态性与痛风患者痛风性肾病的关联。 本研究为病例对照研究，共纳入186名受试者。对照组包含96名健康个体；90名痛风患者被分为两组：组1为45名无痛风性肾病的痛风患者，组2为45名合并痛风性肾病的痛风患者。对各临床分组与对照组之间的SOD2（Ala16Val）、GPX4（C718T）及COL1A1（C1997A）基因多态性的等位基因频率与基因型频率进行比较。统计学分析采用χ²检验、比值比（OR）及p值进行统计推断。 研究结果显示，SOD2 Ala16Val基因多态性与痛风性肾病患者的关联最为显著。在组2中，Ala等位基因表现出保护性关联（χ²=8.81；p=0.003；OR=0.34），而Val等位基因则与肾病发病风险升高相关（χ²=8.81；p=0.003；OR=2.95）。Ala/Ala基因型同样表现出保护效应（χ²=5.26；p=0.022；OR=0.38），而Val/Val基因型则与肾病发病风险显著升高相关（χ²=5.52；p=0.019；OR=9.27）。针对GPX4 C718T，组2中C等位基因（χ²=4.00；p=0.045；OR=0.60）与T等位基因（χ²=4.00；p=0.045；OR=1.67）的频率存在显著差异，但基因型层面的关联未达到统计学显著性。对于COL1A1 C1997A，组2中C等位基因频率更低（χ²=8.81；p=0.003；OR=0.34），A等位基因频率更高（χ²=8.81；p=0.003；OR=2.95）；C/C基因型具有保护效应（χ²=5.26；p=0.022；OR=0.38），而A/A基因型则与肾病发病风险显著相关（χ²=5.52；p=0.019；OR=9.27）。 研究结果表明，SOD2（Ala16Val）、GPX4（C718T）及COL1A1（C1997A）基因多态性与痛风患者发生痛风性肾病的易感性相关，其中SOD2 Ala16Val的关联强度最高。本研究结果支持分子遗传标志物在识别肾脏受累风险升高的痛风患者中的潜在应用价值。