International dental journal · 2024
Association Between Autoimmune Thyroid disease and Oral Lichen Planus: A Multi-Omic Genetic Analysis.
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Ni Jie, Ye Xinjian, Chen Yitong, Fu Haizhou, Wu Ziqiong, Lu Haiping, Chen Qianming
Аннотация
OBJECTIVE: The oral mucosa mirrors a range of latent systemic disorders, with potential clinical associations noted between autoimmune thyroid disease (AITD) and oral lichen planus (OLP). This study aims to explore the genetic relationship and underlying mechanisms mediating these conditions.
METHODS: A 2-step Mendelian randomization (MR) analysis was conducted to elucidate the genetic relationship and mediating factors between AITD and OLP. Linkage disequilibrium score regression was employed to assess heritability and genetic correlations among phenotypes, followed by genetic colocalization analysis to discern shared genetic variants. A transcriptome-wide association study (TWAS) was also performed to pinpoint gene expression profiles.
RESULTS: Genetically predicted AITD is associated with an increased risk of OLP (OR[95% CI]: 1.44[1.19,1.74], P=1.61 × 10-4), potentially mediated by hypothyroidism. There is strong evidence of colocalization between AITD and OLP, with a shared PTPN22 gene variant driving this association. TWAS further identified RNASET2 and FGFR1OP within the HLA region as high-confidence shared genes for both conditions.
CONCLUSION: Our study provides novel evidence of a possible genetic association between AITD and OLP. These findings highlight the critical role of endocrine alterations in maintaining oral immune homeostasis, though further research is warranted to validate our findings.
METHODS: A 2-step Mendelian randomization (MR) analysis was conducted to elucidate the genetic relationship and mediating factors between AITD and OLP. Linkage disequilibrium score regression was employed to assess heritability and genetic correlations among phenotypes, followed by genetic colocalization analysis to discern shared genetic variants. A transcriptome-wide association study (TWAS) was also performed to pinpoint gene expression profiles.
RESULTS: Genetically predicted AITD is associated with an increased risk of OLP (OR[95% CI]: 1.44[1.19,1.74], P=1.61 × 10-4), potentially mediated by hypothyroidism. There is strong evidence of colocalization between AITD and OLP, with a shared PTPN22 gene variant driving this association. TWAS further identified RNASET2 and FGFR1OP within the HLA region as high-confidence shared genes for both conditions.
CONCLUSION: Our study provides novel evidence of a possible genetic association between AITD and OLP. These findings highlight the critical role of endocrine alterations in maintaining oral immune homeostasis, though further research is warranted to validate our findings.