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Association of ABCG1 gene methylation and its dynamic change status with incident type 2 diabetes mellitus: the Rural Chinese Cohort Study

Journal of Human Genetics volume 66, pages 347–357 (2021)Cite this article

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Abstract

To explore whether DNA methylation of the ATP-binding cassette G1 (ABCG1) gene and its dynamic change are associated with incident type 2 diabetes mellitus (T2DM). We conducted a nested case–control study with 286 pairs of T2DM cases and matched controls nested in the Rural Chinese Cohort Study. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for incident T2DM risk according to ABCG1 methylation level at baseline and its dynamic change at follow-up examination. Spearman’s rank correlation coefficients were used to analyze the association between ABCG1 methylation and its possible risk factors in the control group. We found that T2DM risk increased by 16% (OR = 1.16, 95% CI = 1.02–1.31) with each 1% increase in DNA methylation levels of the ABCG1 loci CpG13 and CpG14. DNA methylation change of the ABCG1 locus CpG15 during the 6-year follow-up was associated with increased T2DM risk: T2DM risk increased by 78% in the upper tertile group (methylation gain ≥5%) versus lower tertile group (methylation gain <1%) (OR = 1.78, 95% CI = 1.01–3.15). Furthermore, body mass index was positively correlated with the DNA methylation level of the ABCG1 loci CpG13, CpG14 and CpG15. In conclusion, DNA methylation levels of the ABCG1 loci CpG13 and CpG14 and the methylation gain of locus CpG15 were positively associated with incident T2DM risk, which may suggest a possible etiologic pattern for T2DM and potentially improve T2DM prediction in rural Chinese people.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant nos. 81402752 and 81673260); the Natural Science Foundation of Guangdong Province (Grant no 2019A1515011183); and the Science and Technology Development Foundation of Shenzhen (Grant nos. JCYJ20170412110537191 and JCYJ20190808145805515). The investigators are grateful to the dedicated participants and all research staff of the study.

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Authors and Affiliations

  1. Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen Univerity Health Science Center, Shenzhen, PR China

    Ranran Qie, Pei Qin, Qionggui Zhou, Yanyan Zhang, Xiaoyan Wu, Yuying Wu, Yang Li, Dongsheng Hu & Ming Zhang

  2. Department of Mental Health, Bao’an Chronic Diseases Prevent and Cure Hospital, Shenzhen, PR China

    Qing Chen

  3. Key Lab of Epidemiology, Department of Infectious Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, PR China

    Tieqiang Wang

  4. Key Lab of Epidemiology, Department of Chronic Disease Control and Prevention, Shenzhen Guangming District Center for Disease Control and Prevention, Shenzhen, PR China

    Xiaoliang Chen

  5. Study Team of Shenzhen’s Sanming Project, The Affiliated Luohu Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong, PR China

    Jian Wang, Ruirong Cheng & Jinchun Lin

  6. Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China

    Yang Zhao, Dechen Liu, Cheng Cheng, Leilei Liu, Quanman Li, Chunmei Guo, Gang Tian, Minghui Han, Shengbing Huang, Xingjin Yang, Yang Zhao, Yifei Feng & Dongsheng Hu

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  1. Ranran Qie
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Contributions

RQ, DH, and MZ substantially contributed to the design and drafting of the study and the analysis and interpretation of the data. QC, TW, XC, JW, RC, JL, YZ, DL, PQ, CC, LL, QL, CG, QZ, GT, MH, SH, YZ, XW, YW, YL, XY, YZ, YF, DH, and MZ revised it critically for important intellectual content. All authors were involved in the collection of data and approval of the final version of the manuscript.

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Correspondence to Ming Zhang.

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Qie, R., Chen, Q., Wang, T. et al. Association of ABCG1 gene methylation and its dynamic change status with incident type 2 diabetes mellitus: the Rural Chinese Cohort Study. J Hum Genet 66, 347–357 (2021). https://doi.org/10.1038/s10038-020-00848-z

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