在日本系统性红斑狼疮患者中对 和 XL9 区域变异体的遗传剖析： 的主要作用。
Genetic dissection of and XL9 region variants in Japanese patients with systemic lupus erythematosus: primary role for .
机构信息
Molecular and Genetic Epidemiology Laboratory, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
Master's Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
出版信息
RMD Open. 2023 May;9(2). doi: 10.1136/rmdopen-2023-003214.
OBJECTIVE
Major histocompatibility complex strongly contributes to susceptibility to systemic lupus erythematosus (SLE). In the European populations, and are susceptibility alleles, but locus was reported to account for the association of . With respect to , strong linkage disequilibrium with a variant rs2105898T in the XL9 region, located between and and regulates HLA-class II expression levels, was reported; however, the causative allele remains to be determined. Leveraging the genetic background of the Japanese population, where and are commonly present and only is associated with SLE, this study aimed to distinguish the genetic contribution of and XL9 variants.
METHODS
Among the XL9 variants, two (rs2105898 and rs9271593) previously associated variants in the European populations and two (rs9271375 and rs9271378) which showed a trend towards association in a Japanese Genome-Wide Association Study were selected. Associations of the XL9 variants and were examined in 442 Japanese SLE patients and 779 controls. Genotyping of the XL9 variants was performed by TaqMan SNP Genotyping Assay and direct sequencing. alleles were determined by PCR-reverse sequence-specific oligonucleotide probes.
RESULTS
Among the XL9 variants, associations of rs2105898T and rs9271593C were replicated in the Japanese population. However, these associations became no longer significant when conditioned on . In contrast, the association of remained significant after conditioning on the XL9 variants.
CONCLUSION
In the Japanese population, was found to be primarily associated with SLE, and to account for the apparent association of XL9 region.
目的
主要组织相容性复合体强烈影响系统性红斑狼疮（SLE）的易感性。在欧洲人群中，和是易感等位基因，但位点被报道与有关。关于，在位于和之间的 XL9 区域中，报道了与变体 rs2105898T 之间存在强连锁不平衡，该变体调节 HLA-Ⅱ类表达水平；然而，致病等位基因仍有待确定。利用日本人群的遗传背景，其中和普遍存在，而仅与 SLE 相关，本研究旨在区分和 XL9 变体的遗传贡献。
方法
在 XL9 变体中，选择了两个先前在欧洲人群中与变体相关的变体（rs2105898 和 rs9271593），以及两个在日本全基因组关联研究中显示出关联趋势的变体（rs9271375 和 rs9271378）。在 442 名日本 SLE 患者和 779 名对照中检查了 XL9 变体和的关联。通过 TaqMan SNP 基因分型测定和直接测序对 XL9 变体进行基因分型。通过 PCR-反向序列特异性寡核苷酸探针确定等位基因。
结果
在 XL9 变体中，rs2105898T 和 rs9271593C 的关联在日本人群中得到复制。然而，当条件为时，这些关联变得不再显著。相比之下，在条件为 XL9 变体时，的关联仍然显著。
结论
在日本人群中，被发现主要与 SLE 相关，并解释了 XL9 区域的明显关联。
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