Association Between Autoimmune Thyroid disease and Oral Lichen Planus: A Multi-Omic Genetic Analysis

Jie Ni; Xinjian Ye; Yitong Chen; Haizhou Fu; Ziqiong Wu; Haiping Lu; Qianming Chen

doi:10.1016/j.identj.2024.12.014

Association Between Autoimmune Thyroid disease and Oral Lichen Planus: A Multi-Omic Genetic Analysis

Int Dent J. 2024 Dec 30:S0020-6539(24)01634-4. doi: 10.1016/j.identj.2024.12.014. Online ahead of print.

Authors

Jie Ni¹, Xinjian Ye¹, Yitong Chen², Haizhou Fu², Ziqiong Wu², Haiping Lu², Qianming Chen³

Affiliations

¹ Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China.
² School of Stomatology, Zhejiang Chinese Medical University, Hangzhou, China.
³ Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China. Electronic address: qmchen@zju.edu.cn.

PMID: 39741066
DOI: 10.1016/j.identj.2024.12.014

Abstract

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.

Keywords: Autoimmune thyroid disease; Genetic correlation; Mendelian randomization; Multi-omic analysis; Oral lichen planus; Transcriptome-wide association study.