Feng Weimin, Wang Ke, Yang Ziyao, Yang Yu, Chen Yanli, Cui Liyan, Zhao Xiaotao
Clin Lab. 2025 Aug 1;71(8). doi: 10.7754/Clin.Lab.2025.241222.
Uric acid, the final product of purine metabolism, is primarily excreted through the kidneys and intestines. Dysregulation in uric acid production or excretion can result in hyperuricemia and gout. Several proteins play important roles in uric acid metabolism. Among them, GLUT9, a key protein for uric acid excretion, has garnered significant attention, particularly for two SNPs (rs3733591 and rs1014290) on its encoding gene SLC2A9. However, their relationship with gout and hyperuricemia in the Han Chinese population has not been researched.
This study investigated 498 individuals, including 300 patients with hyperuricemia or gout and 198 healthy controls. Serum uric acid levels were measured, and the genotypes of rs3733591 and rs1014290 were determined using the multicolor melting curve analysis (MMCA) method. These results were subjected to statistical analysis.
This detection result highlights the value of MMCA as a rapid and accurate method for genotyping rs3733591 and rs1014290. Statistical analysis revealed that the proportion of the wild-type (C) allele at rs3733591 and the mutant (A) allele at rs1014290 were significantly higher in patients with hyperuricemia and gout compared to healthy controls. Additionally, individuals with the homozygous mutant genotype at rs3733591 had significantly lower uric acid levels compared to those with the wild-type and heterozygous genotypes, whereas homozygous mutants of rs1014290 exhibited higher uric acid levels. Among the various models based on clinical and laboratory data from 433 participants, the logistic regression model based on eight factors - gender, age, eGFR, WBC, HDL, MCHC, rs3733591, and rs1014290 - demonstrated the best diagnostic performance for gout and hyperuricemia, achieving an AUC of 0.8737.
In conclusion, this study demonstrated a close association between SLC2A9 gene polymorphisms and gout as well as hyperuricemia in the Han Chinese population. Furthermore, the SLC2A9 gene polymorphisms could serve as key parameters for diagnosing these conditions.
尿酸是嘌呤代谢的终产物，主要通过肾脏和肠道排泄。尿酸生成或排泄的失调可导致高尿酸血症和痛风。几种蛋白质在尿酸代谢中起重要作用。其中，尿酸排泄的关键蛋白GLUT9受到了广泛关注，尤其是其编码基因SLC2A9上的两个单核苷酸多态性（SNPs，rs3733591和rs1014290）。然而，它们与汉族人群痛风和高尿酸血症的关系尚未得到研究。
本研究调查了498名个体，包括300例高尿酸血症或痛风患者和198名健康对照。测量血清尿酸水平，并使用多色熔解曲线分析（MMCA）方法确定rs3733591和rs1014290的基因型。对这些结果进行统计分析。
该检测结果突出了MMCA作为一种快速准确的rs3733591和rs1014290基因分型方法的价值。统计分析显示，与健康对照相比，高尿酸血症和痛风患者中rs3733591的野生型（C）等位基因和rs1014290的突变型（A）等位基因的比例显著更高。此外，rs3733591纯合突变基因型个体的尿酸水平显著低于野生型和杂合基因型个体，而rs1014290纯合突变体的尿酸水平较高。在基于433名参与者的临床和实验室数据的各种模型中，基于性别、年龄、估算肾小球滤过率（eGFR）、白细胞（WBC）、高密度脂蛋白（HDL）、平均红细胞血红蛋白浓度（MCHC）、rs3733591和rs1014290这八个因素的逻辑回归模型对痛风和高尿酸血症的诊断性能最佳，曲线下面积（AUC）为0.8737。
总之，本研究表明汉族人群中SLC2A9基因多态性与痛风和高尿酸血症密切相关。此外，SLC2A9基因多态性可作为诊断这些疾病的关键参数。
