Differential Association of Mitochondrial DNA Haplogroups J and H With the Methylation Status of Articular Cartilage: Potential Role in Apoptosis and Metabolic and Developmental Processes.
Arthritis Rheumatol
; 71(7): 1191-1200, 2019 07.
Article
in En
| MEDLINE
| ID: mdl-30747498
ABSTRACT
OBJECTIVE:
To analyze the influence of mitochondrial genome variation on the DNA methylome of articular cartilage.METHODS:
DNA methylation profiling was performed using data deposited in the NCBI Gene Expression Omnibus database (accession no. GSE43269). Data were obtained for 14 cartilage samples from subjects with haplogroup J and 20 cartilage samples from subjects with haplogroup H. Subsequent validation was performed in an independent subset of 7 subjects with haplogroup J and 9 with haplogroup H by RNA-seq. Correlated genes were validated by real-time polymerase chain reaction in an independent cohort of 12 subjects with haplogroup J and 12 with haplogroup H. Appropriate analyses were performed using R Bioconductor and qBasePlus software, and gene ontology analysis was conducted using DAVID version 6.8.RESULTS:
DNA methylation profiling revealed 538 differentially methylated loci, while whole-transcriptome profiling identified 2,384 differentially expressed genes, between cartilage samples from subjects with haplogroup H and those with haplogroup J. Seventeen genes showed an inverse correlation between methylation and expression. In terms of gene ontology, differences in correlations between methylation and expression were also detected between cartilage from subjects with haplogroup H and those with haplogroup J, highlighting a significantly enhanced apoptotic process in cartilage from subjects with haplogroup H (P = 0.007 for methylation and P = 0.019 for expression) and repressed apoptotic process in cartilage from subjects with haplogroup J (P = 0.021 for methylation), as well as a significant enrichment of genes related to metabolic processes (P = 1.93 × 10-4 for methylation and P = 6.79 x 10-4 for expression) and regulation of gene expression (P = 0.012 for methylation) in cartilage from subjects with haplogroup H, and to developmental processes (P = 0.015 for methylation and P = 8.25 x 10-12 for expression) in cartilage from subjects with haplogroup J.CONCLUSION:
Mitochondrial DNA variation differentially associates with the methylation status of articular cartilage by acting on key mechanisms involved in osteoarthritis, such as apoptosis and metabolic and developmental processes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Mitochondrial
/
Cartilage, Articular
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Apoptosis
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Osteoarthritis, Knee
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Epigenome
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Arthritis Rheumatol
Year:
2019
Document type:
Article
Affiliation country:
Spain