Author:
Campagna Maria Pia,Xavier Alexandre,Stankovich Jim,Maltby Vicki E.,Slee Mark,Yeh Wei Z.,Kilpatrick Trevor,Scott Rodney J.,Butzkueven Helmut,Lechner-Scott Jeannette,Lea Rodney A.,Jokubaitis Vilija G.
Abstract
Abstract
Background
Pregnancy in women with multiple sclerosis (wwMS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and/or central nervous system function. In this study, we aimed to identify whole blood and immune cell-specific DNA methylation patterns associated with parity in relapse-onset MS.
Results
We investigated the association between whole blood and immune cell-type-specific genome-wide methylation patterns and parity in 192 women with relapse-onset MS, matched for age and disease severity. The median time from last pregnancy to blood collection was 16.7 years (range = 1.5–44.4 years). We identified 2965 differentially methylated positions in whole blood, 68.5% of which were hypermethylated in parous women; together with two differentially methylated regions on Chromosomes 17 and 19 which mapped to TMC8 and ZNF577, respectively. Our findings validated 22 DMPs and 366 differentially methylated genes from existing literature on epigenetic changes associated with parity in wwMS. Differentially methylated genes in whole blood were enriched in neuronal structure and growth-related pathways. Immune cell-type-specific analysis using cell-type proportion estimates from statistical deconvolution of whole blood revealed further differential methylation in T cells specifically (four in CD4+ and eight in CD8+ T cells). We further identified reduced methylation age acceleration in parous women, demonstrating slower biological aging compared to nulligravida women.
Conclusion
Differential methylation at genes related to neural plasticity offers a potential molecular mechanism driving the long-term effect of pregnancy on MS outcomes. Our results point to a potential ‘CNS signature’ of methylation in peripheral immune cells, as previously described in relation to MS progression, induced by parity. As the first epigenome-wide association study of parity in wwMS reported, validation studies are needed to confirm our findings.
Funder
MSRA Project Grant
RMH Home Lottery Grant
Pennycook Foundation Grant 2018
MSBase Foundation Project Grant
Charity Works for MS Project Grant
Monash University Project Grant
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
Cited by
1 articles.
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