Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia

Abstract 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...

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Main Authors: Meiting Liang, Xingxing Liu, Meng Sun, Jun Zhu, Shanshan Yang, FuRong Jing, Jingyi Shen, Yi He, Wujin Chen, Yuping Sun, Yongsheng Li
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-93312-x
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author Meiting Liang
Xingxing Liu
Meng Sun
Jun Zhu
Shanshan Yang
FuRong Jing
Jingyi Shen
Yi He
Wujin Chen
Yuping Sun
Yongsheng Li
author_facet Meiting Liang
Xingxing Liu
Meng Sun
Jun Zhu
Shanshan Yang
FuRong Jing
Jingyi Shen
Yi He
Wujin Chen
Yuping Sun
Yongsheng Li
author_sort Meiting Liang
collection DOAJ
description Abstract 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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spelling doaj-art-6e27466adea84ede9624f6c7ec49306f2025-08-20T03:41:40ZengNature PortfolioScientific Reports2045-23222025-03-011511910.1038/s41598-025-93312-xAnalysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemiaMeiting Liang0Xingxing Liu1Meng Sun2Jun Zhu3Shanshan Yang4FuRong Jing5Jingyi Shen6Yi He7Wujin Chen8Yuping Sun9Yongsheng Li10Department of Pathology, School of Basic Medical Sciences, XinJiang Second Medical CollegeLaboratory and Equipment Management Center of Xinjiang Second Medical CollegeDepartment of Pathology, School of Basic Medical Sciences, XinJiang Second Medical CollegeDepartment of Pathology, School of Basic Medical Sciences, XinJiang Second Medical CollegeDepartment of Laboratory Medicine, Fifth Affiliated Hospital of Xinjiang Medical UniversityDepartment of Pathology, School of Basic Medical Sciences, XinJiang Second Medical CollegeDepartment of Pathology, School of Basic Medical Sciences, XinJiang Second Medical CollegeDepartment of Cell and Genetics, Xinjiang Second Medical CollegeDepartment of Morphological Center, School of Basic Medical Sciences, Xinjiang Medical UniversityDepartent of Microbiology, School of Basic Medical Sciences, Xinjiang Medical UniversityDepartment of Preventive Medicine, Medical College, Tarim UniversityAbstract 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.https://doi.org/10.1038/s41598-025-93312-xABCG2rs2231142 locusSingle nucleotide polymorphismHyperuricemia
spellingShingle Meiting Liang
Xingxing Liu
Meng Sun
Jun Zhu
Shanshan Yang
FuRong Jing
Jingyi Shen
Yi He
Wujin Chen
Yuping Sun
Yongsheng Li
Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
Scientific Reports
ABCG2
rs2231142 locus
Single nucleotide polymorphism
Hyperuricemia
title Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
title_full Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
title_fullStr Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
title_full_unstemmed Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
title_short Analysis of ABCG2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
title_sort analysis of abcg2 gene rs2231142 single nucleotide polymorphism and risk factors in hyperuricemia
topic ABCG2
rs2231142 locus
Single nucleotide polymorphism
Hyperuricemia
url https://doi.org/10.1038/s41598-025-93312-x
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