Case-only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD-2353F22.1 implying the importance of periodontal wound healing for disease aetiology.
Case-only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD-2353F22.1 implying the importance of periodontal wound healing for disease aetiology.
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仅病例设计确定了 SIGLEC5 和 PLG 的遗传风险变异与 lncRNA CTD-2353F22 1 的相互作用，这意味着牙周伤口愈合对于疾病病因学的重要性
DOI：
10.1111/jcpe.13712
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发表时间：
2022
影响因子：
6.7
通讯作者：
Schaefer AS
中科院分区：
文献类型：
--
作者：
Mueller R;Freitag-Wolf S;Weiner J 3rd;Chopra A;Dommisch H;Schaefer AS
目的牙周炎表型变异的基础是遗传变异。个体风险等位基因的疾病相关效应被认为是遗传交互作用的结果。我们研究了 × 基因(G×G)与牙周炎易感等位基因的相互作用。材料与方法我们采用病例设计，研究了我们最近的全基因组关联研究和 5 × 10−6的Meta分析中显示的单核苷酸多态。结果唾液酸结合Ig样凝集素5(SIGLEC5)和纤溶酶原(PLG)基因上的SNP与rs1122900在长非编码RNA(LncRNA)CTD-2353F22上存在G×G相互作用。相关染色质顺式激活的CTD-2353F22.16.5倍(p=0.003)，表明CTD-2353F22.1为该interaction.CTD‐2353F22.1regulatedGADD45A(padj<； 4.9 × 10−11，的靶基因log2倍变化(Fc)，THBS1，SERPINE1和组织因子F3(PADJ<； 5 × 10−7，log2FC ≥ −0.35)和基因集“血管生成”(曲线下面积=0.71，PADJ=8.2 × 10−5)。Rs1122900效应的C等位基因降低了报告基因活性(5.5倍，p=0.0003)和PRDM14结合率(76%)。结论CTD-2353F221介导SIGLEC5和PLG的相互作用，以及在牙周创伤愈合中起作用的基因。
AimThe basis of phenotypic variation of periodontitis is genetic variability. Disease relevant effects of individual risk alleles are considered to result from genetic interactions. We investigated gene × gene (G×G) interactions of suggestive periodontitis susceptibility alleles.Materials and MethodsWe used the case‐only design and investigated single‐nucleotide polymorphism (SNPs) that showed associations in our recent genome‐wide association study (GWAS) and GWAS meta‐analysis withp< 5 × 10−6. CRISPR‐dCas9 gene activation followed by RNA‐sequencing and gene‐set enrichment analyses elucidated differentially expressed genes and gene networks. With the databases of SNPInspector and Transfac professional, luciferase reporter gene assays and antibody electrophoretic mobility shift experiments, we analysed allele‐specific effects on transcription factor binding.ResultsSNPs at the genes sialic acid binding Ig‐like lectin 5 (SIGLEC5) and plasminogen (PLG) showed G×G interactions with rs1122900 at the long non‐coding RNA (lncRNA)CTD‐2353F22. Associated chromatin cis‐activatedCTD‐2353F22.16.5‐fold (p= .003), indicatingCTD‐2353F22.1as target gene of this interaction.CTD‐2353F22.1regulatedGADD45A(padj< 4.9 × 10−11, log2fold change (FC) = −0.55),THBS1,SERPINE1andTissue Factor F3(padj< 5 × 10−7, log2FC ≥ −0.35) and the gene set “angiogenesis” (area under the curve = 0.71,padj= 8.2 × 10−5). rs1122900 effect C‐allele decreased reporter gene activity (5.5‐fold,p= .0003) and PRDM14 binding (76%).ConclusionsCTD‐2353F22.1mediates interaction ofSIGLEC5andPLG, together with genes that function in periodontal wound healing.
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