Association of ABCG2 gene variants with urate levels in Mexican patients with type 2 diabetes and chronic kidney disease

ABCG2基因变异与墨西哥2型糖尿病合并慢性肾病患者尿酸水平的相关性

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Abstract

The contribution of ABCG2 gene variants to hyperuricemia in Mexican patients with type 2 diabetes (T2D) remains uncertain, despite previously established associations in other populations. In this study, we analyzed the association of the ABCG2 gene variants rs2054576, rs2231142 and rs1001796 with serum uric acid (SUA) levels and hyperuricemia in patients with T2D and chronic kidney disease (CKD) from Mexico. This cross-sectional study involved the genotyping of 1,085 Mexican patients with T2D and 284 healthy subjects (HS) for the missense variant Q141K (rs2231142) and two intronic variants, rs2054576, and rs10011976 of the ABCG2 gene. Univariate and multivariate analyses were conducted to examine the association between ABCG2 genotypes and urate levels and hyperuricemia in relation to the presence of CKD. Clinical and biochemical parameters were also determined and compared. Serum uric acid concentrations and prevalence of hyperuricemia were higher in the patient group compared to healthy subjects. In the patient population, individuals with CKD demonstrated elevated SUA levels and a greater prevalence of hyperuricemia when compared to those without CKD (6.4 mg/dL vs. 5.0 mg/dL, p < 0.001 and 49% vs. 19%, p < 0.001), respectively). The rs2231142 variant showed a significant association with SUA concentrations among patients with T2D (β = 0.393; p = 0.017), as well as healthy individuals (β = 0.407; p = 0.005); however, no significant association was observed with hyperuricemia. In this cohort of Mexican patients with T2D, kidney disease was found as the primary factor associated with hyperuricemia. Additionally, rs2231142 was the only ABCG2 gene variant linked to SUA levels in both T2D patients and healthy individuals, though it was not associated with hyperuricemia. Nevertheless, genetic analysis of rs2231142 may contribute to the evaluation of T2D patients at risk for complications related to elevated uric acid. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-35853-3.

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