Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
Molecular Genetics and Bioinformatics Laboratory, School of Medicine, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil.
Cells. 2023 Feb 15;12(4):630. doi: 10.3390/cells12040630.
Vitiligo is the most frequent cause of depigmentation worldwide. Genetic association studies have discovered about 50 loci associated with disease, many with immunological functions. Among them is HLA-G, which modulates immunity by interacting with specific inhibitory receptors, mainly LILRB1 and LILRB2. Here we investigated the and association with vitiligo risk and evaluated the possible role of interactions between HLA-G and its receptors in this pathogenesis. We tested the association of the polymorphisms of , , and with vitiligo using logistic regression along with adjustment by ancestry. Further, methods based on the multifactor dimensionality reduction (MDR) approach (MDR v.3.0.2, GMDR v.0.9, and MB-MDR) were used to detect potential epistatic interactions between polymorphisms from the three genes. An interaction involving rs9380142 and rs2114511 polymorphisms was identified by all methods used. The polymorphism rs9380142 is an 3'UTR variant (+3187) with a well-established role in mRNA stability. The polymorphism rs2114511 is located in the exonic region of . Although no association involving this SNP has been reported, ChIP-Seq experiments have identified this position as an EBF1 binding site. These results highlight the role of an epistatic interaction between and in vitiligo pathogenesis.
白癜风是全球最常见的色素减退性疾病。遗传关联研究已经发现了约 50 个与疾病相关的位点，其中许多具有免疫功能。其中包括 HLA-G，它通过与特定的抑制性受体（主要是 LILRB1 和 LILRB2）相互作用来调节免疫。在这里，我们研究了 和 与白癜风风险的关联，并评估了 HLA-G 及其受体之间相互作用在发病机制中的可能作用。我们使用逻辑回归结合祖先调整，测试了 、 和 多态性与白癜风的关联。此外，还使用多因素维度缩减（MDR）方法（MDR v.3.0.2、GMDR v.0.9 和 MB-MDR）检测来自三个基因的多态性之间潜在的上位性相互作用。所有使用的方法都鉴定出了 rs9380142 和 rs2114511 多态性之间的相互作用。rs9380142 是一个 3'UTR 变体（+3187），其在 mRNA 稳定性方面具有明确的作用。rs2114511 位于 的外显子区域。虽然没有报道涉及该 SNP 的关联，但 ChIP-Seq 实验已经确定了该位置是 EBF1 结合位点。这些结果强调了 与 之间上位性相互作用在白癜风发病机制中的作用。
