Sex and Gender in Rheumatoid Arthritis: Considering a Risk Factor Hierarchy

Abstract

Is sex or gender a greater risk factor for Rheumatoid Arthritis (RA)? Identifying how gender and sex mediate RA is important because women and females make up the majority of RA patients. Additionally, rheumatoid arthritis is a serious immune disease that greatly affects an individual’s quality of life. The reason behind the difference in RA diagnosis by gender and sex is important to guide how the difference can be mitigated. In this study, it is hypothesized that susceptibility to RA is mediated more by factors associated with sex, rather than behavioral and environmental factors associated with gender. Females are more susceptible to autoimmune diseases due to the skewed inactivation that can occur when half of the x-chromosome genetic material, which plays a role in the immune response, is silenced. During skewed inactivation, maternal and paternal x-chromosomes are not silenced in the same proportions, leading to two different self-antigens that cause a stronger immune response and can react to each other, which can produce an auto immunological response, such as RA. A secondary data analysis was performed using the National Library of Medicine database to search for genetic, behavioral, and environmental risk factors that were measured using an odds ratio. The behavioral and environmental risk factor odds ratio was compared to the skewed x-linked odds ratio to compare the effects of sex and gender. It was determined that there are greater odds that RA will be mediated by skewed x-linked chromosomal inactivation than any individual aspect of gender, however there is room for uncertainty regarding whether if either sex or gender definitively has a greater impact on RA diagnosis.