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The effect of ABCA1 gene DNA methylation on blood pressure levels in a Chinese hyperlipidemic population

Journal of Human Hypertension volume 35, pages 1139–1148 (2021)Cite this article

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Abstract

Hypertension is an important public health challenge worldwide. Epigenetic studies are providing novel insight into the underlying mechanisms of hypertension. We investigated the effect of DNA methylation in ATP-binding cassette transporter 1 (ABCA1) gene on blood pressure levels in a Chinese hyperlipidemic population. We randomly selected 211 individuals with hyperlipidemia who had not received any lipid-lowering treatment at baseline from our previous statin pharmacogenetics study (n = 734). DNA methylation loci at the ABCA1 gene were measured by MethylTarget, a next generation bisulfite sequencing-based multiple targeted cytosine-guanine dinucleotide methylation analysis method. Mean DNA methylation level was used in statistical analysis. In all subjects, higher mean ABCA1_B methylation was positively associated with systolic blood pressure (SBP) (β = 8.27, P = 0.008; β = 8.78, P = 0.005) and explained 2.7% and 5.8% of SBP variation before and after adjustment for lipids, respectively. We further divided all patients into three groups based on the tertile of body mass index (BMI) distribution. In the middle tertile of BMI, there was a significantly positive relationship between mean ABCA1_A methylation and SBP (β = 0.89, P = 0.003) and DBP (β = 0.32, P = 0.030). Mean ABCA1_A methylation explained 11.0% of SBP variation and 5.3% of DBP variation, respectively. Furthermore, mean ABCA1_A methylation (β = 0.79; P = 0.007) together with age and gender explained up to 24.1% of SBP variation. Our study provides new evidence that the ABCA1 DNA methylation profile is associated with blood pressure levels, which highlights that DNA methylation might be a significant molecular mechanism involved in the pathophysiological process of hypertension.

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Fig. 1: The ABCA1 gene DNA methylation sequence locus.
Fig. 2: Two CpG islands at the promoter and downstream the first exon of the ABCA1 gene.
Fig. 3: Correlations between SBP and ABCA1_B methylations in overall population (adjusted for age, gender, and BMI).
Fig. 4: Correlations between SBP and ABCA1_A methylations in the middle tertile of BMI population (adjusted for gender and age).
Fig. 5: Correlations between DBP and ABCA1_A methylations in the middle tertile of BMI population (adjusted for gender and age).

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81373484, 81141116 and 30700454); Open fund for Discipline Construction, Institute of Physical Science and Information Technology, Anhui University; and the Academic Top Talents Funding of University (No. gxbjZD2016008). We gratefully acknowledge the assistance and cooperation of the faculty and staff of Anhui Medical University and thank all of the participants in our study.

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Authors and Affiliations

  1. School of Life Sciences, Anhui University, Hefei, China

    Yajie Li, Qian Zhang,  Di Zhang, Qianru Cai, Juanlin Fan & Shanqun Jiang

  2. Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada

    Scott A. Venners

  3. Institute of Biomedicine, Anhui Medical University, Hefei, China

    Shanqun Jiang & Xiping Xu

  4. Department of Cardiology, Peking University First Hospital, Beijing, China

    Jianping Li

  5. National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Xiping Xu

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Contributions

QC and DZ, literature search, collecting data, processing data, data interpretation, analyzing data, writing manuscript; JF, literature search, data interpretation; SV, data interpretation, commenting on manuscript; SJ & JL, study design, data interpretation, writing manuscript; XX, study design, commenting on manuscript. All authors read and approved the final manuscript.

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Correspondence to Shanqun Jiang or Jianping Li.

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All participants provided written informed consent, and the study protocol was approved by the ethics committee of the Institute of Biomedicine, Anhui Medical University. The procedures followed in our study were in accordance with the ethical standards of the Declarations of Helsinki and Istanbul

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Li, Y., Zhang, Q., Di Zhang et al. The effect of ABCA1 gene DNA methylation on blood pressure levels in a Chinese hyperlipidemic population. J Hum Hypertens 35, 1139–1148 (2021). https://doi.org/10.1038/s41371-020-00479-z

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