Association of ABCG2 rs2231142 Allele and BMI With Hyperuricemia in an East Asian Population

Yen-Ju Chen; I-Chieh Chen; Hsueh-Ju Lin; Ying-Cheng Lin; Jui-Chun Chang; Yi-Ming Chen; Tzu-Hung Hsiao; Pei-Chun Chen; Ching-Heng Lin

doi:10.3389/fgene.2021.709887

Association of ABCG2 rs2231142 Allele and BMI With Hyperuricemia in an East Asian Population

Front Genet. 2021 Aug 31:12:709887. doi: 10.3389/fgene.2021.709887. eCollection 2021.

Authors

Yen-Ju Chen^{1

2

3}, I-Chieh Chen¹, Hsueh-Ju Lin¹, Ying-Cheng Lin⁴, Jui-Chun Chang⁵, Yi-Ming Chen^{1

2

6

7}, Tzu-Hung Hsiao^{1

8

9}, Pei-Chun Chen¹⁰, Ching-Heng Lin^{1

8

11

12

13}

Affiliations

¹ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
² Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
³ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁵ Department of Obstetrics and Gynecology and Women's Health, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶ Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
⁷ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸ Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
⁹ Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan.
¹⁰ Department of Mathematics and Information Education, National Taipei University of Education, Taipei, Taiwan.
¹¹ Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
¹² Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan.
¹³ Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

Objectives: Genetic variants and obesity are risk factors for hyperuricemia (HUA). Recent genome-wide association studies have identified ABCG2 rs2231142 as one of the most prominent genetic variants for HUA in an East Asian population. Nevertheless, no large-scale studies have demonstrated any interactive effects between this variant and obesity on serum urate level in Asians. This study aimed to determine the interaction of ABCG2 rs2231142 variant and body mass index (BMI) and its effect on risk of HUA in an East Asian population. Methods: The study was conducted using the Taiwan Biobank database, a population-based biomedical research database of patients with Taiwanese Han Chinese ancestry aged 30-70years between September 2014 and May 2017. Detailed physical information on participants were collected by questionnaires and genotyping using Affymetrix TWB 650K SNP chip. The primary outcome was HUA, defined as a serum uric acid level>7.0mg/dl. Odds ratio (OR) of HUA was analyzed using logistic regression models and the effects of interaction between ABCG2 rs2231142 variants and BMI on serum uric acid level were explored. Results: We identified 25,245 subjects, 4,228 (16.75%) of whom had HUA. The prevalence of HUA was 30% in men and 3.8% in women. The risk of HUA was significantly associated with ABCG2 rs2231142 risk T allele, with more HUA in TT genotype (OR: 2.40, 95% CI: 2.11-2.72, p<0.001) and TG genotype (OR: 1.64, 95% CI: 1.51-1.78, p<0.001) in men, and TT genotype (OR: 2.42, 95% CI: 1.83-3.20, p<0.001) and TG genotype (OR: 1.82, 95% CI: 1.46-2.23, p<0.001) in women, compared with their counterparts. Moreover, we found a strong genetic-environmental interaction associated with the risk of HUA. There was increased risk of HUA by the interaction of ABCG2 rs2231142 variant and BMI for TT genotype (OR: 7.42, 95% CI: 2.54-21.7, p<0.001) and TG genotype (OR: 4.25, 95% CI: 2.13-8.47, p<0.001) in men compared with the GG genotype in men, and for TT genotype (OR: 25.43, 95% CI: 3.75-172.41, p<0.001) and TG genotype (OR: 3.05, 95% CI: 0.79-11.71, p=0.011) in women compared with the GG genotype in women. Conclusion: The risk of HUA was markedly increased by the interaction of ABCG2 rs2231142 variant and BMI, both in men and in women. Body weight control and reduction in BMI are recommended in high-risk patients with the ABCG2 rs2231142 risk T allele.

Keywords: ABCG2 rs2231142; BMI; gout; hyperuricemia; obesity; uric acid.