DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins
Abstract Background To identify nongenetic factors influences on DNA methylation (DNAm) variations associated with blood Alanine Aminotransferase (ALT) concentration, this study conducted an epigenome-wide association study (EWAS) on Chinese monozygotic twins. Methods A total of 61 pairs of Chinese...
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BMC
2025-04-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-025-01869-1 |
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| author | Jingxian Li Jia Luo Tong Wang Xiaocao Tian Chunsheng Xu Weijing Wang Dongfeng Zhang |
| author_facet | Jingxian Li Jia Luo Tong Wang Xiaocao Tian Chunsheng Xu Weijing Wang Dongfeng Zhang |
| author_sort | Jingxian Li |
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| description | Abstract Background To identify nongenetic factors influences on DNA methylation (DNAm) variations associated with blood Alanine Aminotransferase (ALT) concentration, this study conducted an epigenome-wide association study (EWAS) on Chinese monozygotic twins. Methods A total of 61 pairs of Chinese monozygotic twins involved in this study. Whole blood samples were analyzed for DNAm profiling using the Reduced Representation Bisulfite Sequencing (RRBS) technique. We examined the relationship between DNAm levels at each CpG site and serum ALT using a linear mixed-effects model. Enrichment analysis and causal inference analysis was conducted, and differentially methylated regions (DMRs) were further identified. Candidate CpGs were validated in a community sample. Genome-wide significance were calculated by Bonferroni correction (p < 2.14 × 10–7). Results We identified 85 CpGs reaching genome-wide significance (p < 2.14 × 10–7), located in 16 genes including FLT4, ADARB2, MRPS31P2, and RELB. Causal inference suggested that DNAm at 61 out of 85 significant CpGs within 14 genes influenced ALT level. 52 DMRs and 1765 pathways such as low voltage-gated calcium channel activity and focal adhesion were identified having influences on ALT levels. Further validation using community population found four CpGs mapped to FLT4 and three to RELB showing hypomethylation and hypermethylation in cases with abnormal ALT (ALT > 40 U/L), respectively. Conclusion This study identified several differentially methylated CpG sites associated with serum ALT in the Chinese population, particularly within FLT4 and RELB. These findings provide new insights into the epigenetic modifications underlying liver function. |
| format | Article |
| id | doaj-art-cffacb8a04c0486e88370fab45b2e6c5 |
| institution | OA Journals |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | Clinical Epigenetics |
| spelling | doaj-art-cffacb8a04c0486e88370fab45b2e6c52025-08-20T02:10:53ZengBMCClinical Epigenetics1868-70832025-04-0117111410.1186/s13148-025-01869-1DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twinsJingxian Li0Jia Luo1Tong Wang2Xiaocao Tian3Chunsheng Xu4Weijing Wang5Dongfeng Zhang6Department of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityQingdao Municipal Centre for Disease Control and PreventionQingdao Municipal Centre for Disease Control and PreventionDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityDepartment of Epidemiology and Health Statistics, The School of Public Health of Qingdao UniversityAbstract Background To identify nongenetic factors influences on DNA methylation (DNAm) variations associated with blood Alanine Aminotransferase (ALT) concentration, this study conducted an epigenome-wide association study (EWAS) on Chinese monozygotic twins. Methods A total of 61 pairs of Chinese monozygotic twins involved in this study. Whole blood samples were analyzed for DNAm profiling using the Reduced Representation Bisulfite Sequencing (RRBS) technique. We examined the relationship between DNAm levels at each CpG site and serum ALT using a linear mixed-effects model. Enrichment analysis and causal inference analysis was conducted, and differentially methylated regions (DMRs) were further identified. Candidate CpGs were validated in a community sample. Genome-wide significance were calculated by Bonferroni correction (p < 2.14 × 10–7). Results We identified 85 CpGs reaching genome-wide significance (p < 2.14 × 10–7), located in 16 genes including FLT4, ADARB2, MRPS31P2, and RELB. Causal inference suggested that DNAm at 61 out of 85 significant CpGs within 14 genes influenced ALT level. 52 DMRs and 1765 pathways such as low voltage-gated calcium channel activity and focal adhesion were identified having influences on ALT levels. Further validation using community population found four CpGs mapped to FLT4 and three to RELB showing hypomethylation and hypermethylation in cases with abnormal ALT (ALT > 40 U/L), respectively. Conclusion This study identified several differentially methylated CpG sites associated with serum ALT in the Chinese population, particularly within FLT4 and RELB. These findings provide new insights into the epigenetic modifications underlying liver function.https://doi.org/10.1186/s13148-025-01869-1Alanine aminotransferaseCausalityDNA methylationMonozygotic twins |
| spellingShingle | Jingxian Li Jia Luo Tong Wang Xiaocao Tian Chunsheng Xu Weijing Wang Dongfeng Zhang DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins Clinical Epigenetics Alanine aminotransferase Causality DNA methylation Monozygotic twins |
| title | DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins |
| title_full | DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins |
| title_fullStr | DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins |
| title_full_unstemmed | DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins |
| title_short | DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins |
| title_sort | dna methylation associated with the serum alanine aminotransferase concentration evidence from chinese monozygotic twins |
| topic | Alanine aminotransferase Causality DNA methylation Monozygotic twins |
| url | https://doi.org/10.1186/s13148-025-01869-1 |
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