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The relationship between the single nucleotide polymorphism (SNP) at the rs2231142 locus of the Adenosine triphosphate-binding cassette transporter G subfamily member 2 (ABCG2) gene and susceptibility to hyperuricemia (HUA) is to be investigated, alongside an analysis of the associated risk factors for HUA. Venous blood samples were obtained from 1612 patients diagnosed with HUA and 1770 individuals exhibiting normal uric acid (UA) levels. Deoxyribonucleic acid was isolated, followed by amplification of the target gene via polymerase chain reaction. The genotype at the ABCG2 gene rs2231142 locus were determined using the enhanced multiplex ligation detection reaction method. Serum concentrations of UA, glucose, blood urea nitrogen (BUN), creatinine (CREA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) were assessed in both groups. Clinical data were compiled. LASSO regression and multivariate logistic regression analyses were conducted to identify independent risk factors for HUA. A predictive model for HUA that integrates the SNP at the ABCG2 gene rs2231142 locus was developed. The model's accuracy in predicting HUA was evaluated through the receiver operating characteristic (ROC) curve. The frequencies of the GG, GT, and TT genotypes at the rs2231142 locus of the ABCG2 gene in the male control and HUA groups were 66.2% and 60.3%, 29.2% and 35.5%, 4.6% and 4.3% (P = 0.012). These frequencies were markedly different from those of the female control and HUA groups, which exhibited 68.5% and 58.2%, 29.2% and 36.0%, 2.3% and 5.8% (P < 0.001). Regression analysis revealed seven independent risk factors for HUA: waist-to-hip ratio (WHR), BUN, TG, TC, LDL-C, and the rs2231142 G/T and T/T genotypes. For every unit increase in WHR, BUN, TG, and LDL-C, the odds of developing HUA increased by 1.794, 1.166, 1.421, and 1.286 times, respectively. A significant association was found between HUA risk and the rs2231142 G/T and T/T genotypes. Individuals harboring the rs2231142 G/T mutation exhibited a 1.192 times greater likelihood of developing HUA compared to those without the mutation, while those with the T/T genotype had a risk increase of 2.557 times. A diagnostic model for HUA was developed utilizing these risk factors, with performance assessed through the ROC curve. The area under the curve was measured at 74.8%, indicating that the model incorporating the ABCG2 gene rs2231142 locus possesses diagnostic efficacy for early prediction of HUA. Male HUA patients with the TT genotype at the ABCG2 gene rs2231142 locus displayed markedly elevated CREA levels (87.051 ± 36.378 μmol/L) in comparison to homozygous G/G (82.128 ± 39.482 μmol/L) and heterozygous G/T carriers (81.733 ± 35.926 μmol/L). A higher frequency of the T allele mutation at the rs2231142 locus of the ABCG2 gene is observed in HUA patients. Individuals possessing the rs2231142 T allele demonstrate an increased probability of developing HUA, potentially more pronounced in females. The model integrating the rs2231142 T allele locus with associated clinical risk factors exhibits diagnostic efficacy for the early prediction of HUA occurrence. Additionally, the mutation at the ABCG2 gene rs2231142 locus may influence serum CREA levels.
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http://dx.doi.org/10.1038/s41598-025-93312-x | DOI Listing |
J Biochem Mol Toxicol
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Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
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The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
Hyperuricemia (HUA) is a prevalent metabolic disorder driven by dysregulated purine metabolism and impaired urate excretion, and robust animal models are critical for elucidating its pathophysiology and guiding therapy development. This review systematically examines chemically induced, gene-edited, environmental, exercise and microbiota-based HUA models across rodents, poultry, primates, zebrafish and silkworms, highlighting each model's strengths and limitations in mimicking human uric acid handling. We discuss how these models have validated standard urate-lowering treatments-such as xanthine oxidase inhibitors and uricosurics-and uncovered emerging therapeutic targets, including the gut-NLRP3 inflammasome axis and SIRT1-mediated ABCG2 regulation.
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Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, Namiki 1-1, Ibaraki 305-0044, Japan; Graduate School of Science and Technology, University of Tsukuba, Ibaraki 305-8577, Japan. Electronic address:
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View Article and Find Full Text PDFPharmacogenet Genomics
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Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA.
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School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Rivaroxaban is a direct oral anticoagulant (DOAC) that directly inhibits coagulation factor Xa and exerts its anticoagulant effects. Although rivaroxaban generally exhibits predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles, significant interindividual variability in therapeutic responses exists. Research on the role of genetic factors in the clinical variability of rivaroxaban is relatively new and extensive.
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