Abstract
The era of next-generation sequencing has mounted the foundation of many gene expression studies. In rheumatoid arthritis research, this has led to the discovery of important candidate genes which offered novel insights into mechanisms and their possible roles in the cure of the disease. In the last years, data generation has outstripped data analysis and while many studies focused on specific aspects of the disease, a global picture of the disease is not yet accomplished. Here, we analyzed and compared a collection of gene expression information from healthy individuals and from patients suffering under different arthritis conditions from published studies containing the following clinical conditions: early and established rheumatoid arthritis, osteoarthritis and arthralgia. We show comprehensive overviews of this data collection and give new insights specifically on gene expression in the early stage, into sex-dependent gene expression, and we describe general differences in expression of different biotypes of genes. Many genes that are related to cytoskeleton changes (actin filament related genes) are differently expressed in early rheumatoid arthritis in comparison to healthy subjects; interestingly, eight of these genes reverse their expression ratio significantly between men and women compared early rheumatoid arthritis and healthy subjects. There are some slighter changes between men and woman between the conditions early and established rheumatoid arthritis. Another aspect are miRNAs and other gene biotypes which are not only promising candidates for diagnoses but also change their expression grossly in average at rheumatoid arthritis and arthralgia compared to the healthy condition. With a selection of intersecting genes, we were able to generate simple classification models to distinguish between healthy and rheumatoid arthritis as well as between early rheumatoid arthritis to other arthritides based on gene expression.
Highlights
Rheumatoid arthritis (RA) is a chronic, complex, systemic, multifactorial disease [1, 2] with a prevalence of 0.3–1% in the population worldwide [3], affecting women 2–3 times more often than men
Some broader views of gene expression are published based on microarray data [17,18,19], as well as some narrower views based on quantitative polymerase chain reactions (PCRs) of several genes [20,21,22]
The prevalence of RA is lower in men than in women [23,24,25,26], but it is unclear whether this is related to gene expression; reported relations with sex hormones such as estrogen and androgen would be supportive of this hypotheses [27]
Summary
Rheumatoid arthritis (RA) is a chronic, complex, systemic, multifactorial disease [1, 2] with a prevalence of 0.3–1% in the population worldwide [3], affecting women 2–3 times more often than men. There is not one single cause of RA, no single path to progression and no single curative approach, as ultimate success rates of single therapies are limited [8, 9] This has led to the hypothesis that there might be RA subtypes with different RA disease manifestations that are dependent on sex, genotype, gene expression or on the composition of the microbiome, which would make RA an important showcase for personalized medicine. The prevalence of RA is lower in men than in women [23,24,25,26], but it is unclear whether this is related to gene expression; reported relations with sex hormones such as estrogen and androgen would be supportive of this hypotheses [27]. If such major differences of gene expression between men and women exist in RA compared to healthy subjects, these genes might be targets for further investigation as there might be sex-specific issues beside the prevalence
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