Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Public Health, Section of Biostatistics, University of Copenhagen, Denmark; Center for Statistical Science, Peking University, Beijing, China.
Autoimmun Rev. 2019 Apr;18(4):382-392. doi: 10.1016/j.autrev.2018.11.005. Epub 2019 Feb 14.
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.
系统性红斑狼疮（SLE）是一种全身性炎症性自身免疫性疾病，其特征是临床表现和血清学表现广泛。这可能反映了一种复杂的多因素病因，涉及几个已确定的遗传和环境因素，但不能解释 SLE 的全部风险。已确定的 SLE 风险基因型要么非常罕见，要么效应大小适中，并且双胞胎研究表明，除了遗传因素外，SLE 病因中还必须存在其他因素。外显子组包含个体一生中累积的环境影响及其相关的生物学反应。已经证明，暴露于二氧化硅、吸烟和外源性激素可能是 SLE 的环境风险因素，而饮酒似乎具有保护作用。很少有研究调查潜在的基因-环境相互作用，以确定是否有一些未解释的 SLE 风险归因于此。更少的研究关注与 SLE 发病机制相关的特定风险基因型和环境暴露之间的相互作用。队列和病例对照研究可以提供数据来提示这种生物学相互作用，并且各种交互作用的统计措施可以指示这种相互作用的程度。然而，这些研究通常需要非常大的样本量要求，我们认为 SLE 的罕见性在某种程度上可以通过增加对照的比例来补偿。本综述总结了 SLE 中基因-环境相互作用的现有知识体系。我们主张优先考虑包含与 SLE 相关的基因组和外显子组日益详细信息的研究，因为它们有可能揭示 SLE 发病机制的新方面，包括表型异质性。
