Session Information
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Parent-of-origin effects refer to the differential risk or pathogenicity of a disease that depends on the sex of the disease-transmitting parent. Excessive paternal transmission has been described in psoriasis and psoriatic arthritis (PsA) patients. Genomic imprinting or other germ line epigenetic phenomena have been hypothesized to mediate this effect. This study aimed to investigate the presence of germ line epigenetic variants associated with psoriasis and PsA.
Methods: Male psoriasis (n=24) and PsA (n=13) patients were recruited from the University of Toronto Psoriatic Disease Program. Psoriasis patients were diagnosed by a dermatologist and examined by a rheumatologist to verify the absence of PsA. PsA patients were diagnosed by a rheumatologist and satisfied the CASPAR criteria. Unaffected male controls (n=19) with no family history of psoriasis or PsA were also recruited. Sperm cells were isolated from semen samples and genomic DNA was extracted and bisulfite converted. DNA methylation was measured at 485,577 CpG sites using Illumina HumanMethylation 450k arrays. Methylation differences were assessed by Student’s t-test using M-values and then converted to percent differences in methylation (β diff) between groups.
Results: Differential methylation analysis performed on 331,258 unique CpG sites retained after filtering identified 57 differentially methylated CpG sites between psoriasis patients and controls, and 97 between PsA patients and controls (p<0.05). Top hits in psoriasis patients vs. controls included CpG sites near the long non-coding RNA TINCR (β diff=0.14, p=0.03) and IRF6 (β diff=0.16, p=0.03), which are necessary for epidermal differentiation. Top CpG sites in PsA vs. controls were located near LCP1 (β diff=0.16, p=0.01), which regulates polarization and migration of chemokine-stimulated T lymphocytes, and PsA susceptibility locus HLA-B (β diff=-0.25, p=0.03) on 6p21.3. The inflammasome component NLRP13 was differentially methylated in both PsA (β diff=0.11, p=1.8×10-3) and psoriasis (β diff=0.09, p=7.6×10-3) patients compared to controls. There were 84 differentially methylated CpGs between PsA vs. psoriasis patients (p<0.05). Top CpGs were located near TPPP (β diff=0.25, p=1.4×10-4), involved in tubulin polymerization, and HCG26, a non-coding RNA that lies between MICA and MICB on 6p21.3 (β diff=-0.22, p=4.0×10-3). Upon combining the results of all three analyses, five hits mapped to a 2.1 Mb interval on chromosome 8p23.3 that we previously identified as differentially methylated in whole blood of PsA patients with paternally vs. maternally-transmitted disease. Hits in this region were located near the genes ERICH1-AS1, MYOM2, CSMD1, and DLGAP2, which has been computationally identified as a putative paternally imprinted gene.
Conclusion: We identified several differentially methylated CpG sites in the germ line of psoriasis and PsA patients. These preliminary results require further experimental verification and replication in somatic tissues, to determine their relevance to the parent-of-origin effect and the aetiopathogenesis of psoriasis and PsA.
To cite this abstract in AMA style:
Pollock R, O'Reilly D, Rahman P, Chandran V, Gladman D. Germ Line DNA Methylation Profiling Provides Novel Insights into the Parent-of-Origin Effect in Psoriatic Disease [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/germ-line-dna-methylation-profiling-provides-novel-insights-into-the-parent-of-origin-effect-in-psoriatic-disease/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/germ-line-dna-methylation-profiling-provides-novel-insights-into-the-parent-of-origin-effect-in-psoriatic-disease/