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The study of interactions between genome and exposome in the development of systemic lupus erythematosus

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Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by a broad spectrum of clinical and serological manifestations. This may reflect a complex and multifactorial etiology involving several identified genetic and environmental factors, though not explaining the full risk of SLE. Established SLE risk genotypes are either very rare or with modest effect sizes and twin studies indicate that other factors besides genetics must be operative in SLE etiology. The exposome comprises the cumulative environmental influences on an individual and associated biological responses through the lifespan. It has been demonstrated that exposure to silica, smoking and exogenous hormones candidate as environmental risk factors in SLE, while alcohol consumption seems to be protective. Very few studies have investigated potential gene-environment interactions to determine if some of the unexplained SLE risk is attributable hereto. Even less have focused on interactions between specific risk genotypes and environmental exposures relevant to SLE pathogenesis. Cohort and case-control studies may provide data to suggest such biological interactions and various statistical measures of interaction can indicate the magnitude of such. However, such studies do often have very large sample-size requirements and we suggest that the rarity of SLE to some extent can be compensated by increasing the ratio of controls. This review summarizes the current body of knowledge on gene-environment interactions in SLE. We argue for the prioritization of studies that comprise the increasing details available of the genome and exposome relevant to SLE as they have the potential to disclose new aspects of SLE pathogenesis including phenotype heterogeneity.

Original languageEnglish
JournalAutoimmunity Reviews
Volume18
Issue number4
Pages (from-to)382-392
Number of pages11
ISSN1568-9972
DOIs
Publication statusPublished - Apr 2019

    Research areas

  • Case-Control Studies, Environmental Exposure/adverse effects, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome, Human/physiology, Genotype, Humans, Lupus Erythematosus, Systemic/epidemiology

ID: 58901590