The Role of Genetics and Environmental Factors on Autoimmune Disease Incidence With a Focus on Gender Bias in a Family Case Study

Abstract

Most autoimmune diseases disproportionately affect women more than men, with women comprising about 80% of autoimmune disease incidence. The cause for this discrepancy is not known, although there are both genetic and environmental hypotheses. This thesis project aimed to elucidate whether the increased prevalence in women is due to a genetic or environmental factor by analyzing single nucleotide polymorphism (SNP) data from a family of five individuals with a mix of autoimmune diseases (systemic lupus erythematosus (SLE), psoriasis and Hashimoto’s thyroiditis). The overarching hypothesis was that the increased prevalence of autoimmune diseases in women is caused by differing levels of sex hormones due to differing levels of estrogen receptors which can in turn affect vitamin D and calcium levels and affect tight junctions and epithelial barrier integrity. This was examined in the context of the current known literature and SNPs from each member of the family. Each autoimmune disease was looked at and harmful SNPs were analyzed. By comparing and contrasting the male, who has lupus, to the female members of his family, two of which have separate autoimmune diseases and two of which are healthy, differences and similarities in the SNP profile led to the finding of a SNP in the estrogen receptor alpha that is correlated with environmental factors, such as smoking. The male subject, who has lupus, is heterozygous for this polymorphism and so is his female daughter, who does not have lupus. The male subject was a heavy smoker at the time of disease onset and his daughter has never smoked, which may be a reason for the similar SNP profiles but difference in disease onset.