Bang So-Young, Shim Seung Cheol
Division of Rheumatology, Hanyang University Guri Hospital, Guri, Korea.
Hanyang University Institute for Rheumatology Research and Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
J Rheum Dis. 2024 Oct 1;31(4):200-211. doi: 10.4078/jrd.2024.0051. Epub 2024 Jul 23.
The prevalence of systemic lupus erythematosus (SLE) varies significantly based on ethnicity rather than geographic distribution; thus, the prevalence is higher in Asian, Hispanic, and Black African populations than in European populations. The risk of developing lupus nephritis (LN) is the highest among Asian populations. Therefore, we hypothesize that human genetic diversity between races has occurred through the early human migration and human genetic adaptation to various environments, with a particular focus on pathogens. Additionally, we compile the currently available evidence on the ethnic gene diversity of SLE and how it relates to disease severity. The human leukocyte antigen (HLA) locus is well established as associated with susceptibility to SLE; specific allele distributions have been observed across diverse populations. Notably, specific amino acid residues within these HLA loci demonstrate significant associations with SLE risk. The non-HLA genetic loci associated with SLE risk also varies across diverse ancestries, implicating distinct immunological pathways, such as the type-I interferon and janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways in Asians, the type-II interferon signaling pathway in Europeans, and B cell activation pathway in Africans. Furthermore, assessing individual genetic susceptibility using genetic risk scores (GRS) for SLE helps to reveal the diverse prevalence, age of onset, and clinical phenotypes across different ethnicities. A higher GRS increases the risk of LN and the severity of SLE. Therefore, understanding ethnic gene diversity is crucial for elucidating disease mechanisms and SLE severity, which could enable the development of novel drugs specific to each race.
系统性红斑狼疮（SLE）的患病率因种族差异而有显著不同，而非地理分布；因此，亚洲、西班牙裔和非洲黑人人群中的患病率高于欧洲人群。亚洲人群中发生狼疮性肾炎（LN）的风险最高。因此，我们推测种族间的人类遗传多样性是通过早期人类迁徙以及人类对各种环境（特别是病原体）的遗传适应而产生的。此外，我们汇总了目前关于SLE种族基因多样性及其与疾病严重程度关系的现有证据。人类白细胞抗原（HLA）基因座已被充分证实与SLE易感性相关；在不同人群中观察到了特定的等位基因分布。值得注意的是，这些HLA基因座内的特定氨基酸残基与SLE风险存在显著关联。与SLE风险相关的非HLA基因座在不同祖先群体中也有所不同，这涉及不同的免疫途径，例如亚洲人中的I型干扰素和Janus激酶信号转导及转录激活因子（JAK-STAT）途径、欧洲人中的II型干扰素信号通路以及非洲人中的B细胞激活途径。此外，使用SLE的遗传风险评分（GRS）评估个体遗传易感性有助于揭示不同种族间SLE患病率、发病年龄和临床表型的差异。较高的GRS会增加LN风险和SLE的严重程度。因此，了解种族基因多样性对于阐明疾病机制和SLE严重程度至关重要，这可能有助于开发针对每个种族的新型药物。
