Research Paper Volume 13, Issue 3 pp 3843—3865
Cell lineage-specific methylome and genome alterations in gout
- 1 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- 2 Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- 3 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
- 4 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- 5 Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
- 6 Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- 7 Laboratory Diagnosis of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- 8 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- 9 Department of Biological Science and Technology, National Chiao-Tung University, Hsinchu, Taiwan
- 10 Department of Kinesiology, Health and Leisure Studies, National University of Kaohsiung, Kaohsiung, Taiwan
Received: June 10, 2020 Accepted: September 5, 2020 Published: January 20, 2021
https://doi.org/10.18632/aging.202353How to Cite
Copyright: © 2021 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
In this study, we examined data from 69 gout patients and 1,455 non-gout controls using a MethylationEPIC BeadChip assay and Illumina HiSeq platform to identify lineage-specific epigenetic alterations and associated genetic factors that contributed to gouty inflammation. Cell lineage-specific differentially methylated sites were identified using CellDMC after adjusting for sex, age, alcohol drinking, smoking status, and smoking history (total pack-years). Different cell lineages displayed distinct differential methylation. Ingenuity Pathway Analysis and NetworkAnalyst indicated that many differential methylated sites were associated with interleukin-1β expression in monocytes. On the UCSC Genome Browser and WashU Epigenome Browser, metabolic trait, cis-methylation quantitative trait loci, genetic, and functional annotation analyses identified nine methylation loci located in interleukin-1β-regulating genes (PRKCZ, CIDEC, VDAC1, CPT1A, BIRC2, BRCA1, STK11, and NLRP12) that were associated specifically with gouty inflammation. All nine sites mapped to active regulatory elements in monocytes. MoLoTool and ReMap analyses indicated that the nine methylation loci overlapped with binding sites of several transcription factors that regulated interleukin-1β production and gouty inflammation. Decreases in PRKCZ and STK11 methylation were also associated with higher numbers of first-degree relatives who also had gout. The gouty-inflammation specific methylome and genome alterations could potentially aid in the identification of novel therapeutic targets.