Sjögren’s syndrome leading to differential gene expression in males and females and functional impact on the immune system
Concept
The majority of rheumatic diseases are more common in women than in men. Primary Sjögren’s syndrome has among the highest observed female-to-male ratios, and approximately nine out of ten patients with this chronic inflammatory condition are women. This sex-bias remains poorly understood, even though female sex is the strongest known risk factor for Sjögren’s syndrome
Facts and Figures
M Wahren-Herlenius
Karolinska Institute
marie.wahren@ki.se
Meet the Team
University of Bergen
University of Bergen
Harvard Medical School
Objectives
There is no difference in the frequency of the SS-associated genetic polymorphisms between women and men in the general population, yet there is a much higher likelihood for the diseases to develop in women carrying these SNPs compared to men. We therefore hypothesize that the context “female sex” influences the functional impact of the genetic polymorphisms associated with SS differently than the context “male sex”.
Goals/Milestones
Year 1: SNP selection and comprehensive identification of their sex-influenced eQTLs
Year 2 and 3: Sex-influenced transcription factor enrichment to identified gene regions defined
Year 1-3: Gene and pathway confirmation in experimental models
Year 2 and 3: Verification of genes and related pathways in patient-derived tissues
Year 3: Based on data from 1-4, propose at least onetarget or pathway suitable forsex-tailoredpersonalized medicine
Publications
Thorlacius, G.E., Björk, A. & Wahren-Herlenius, M. Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies. Nat Rev Rheumatol (2023). https://doi.org/10.1038/s41584-023-00932-6
Patient Voice
Patient partners trained through the Swedish Rheumatism Association will participate in both project design and during the study. The patient partners will be part of the steering group and participate in discussions on the results and making the most of potential findings. The patient partners will also be involved in the communication with patients and society, including the writing of a plain language summary of the project and main findings.