Impact of periodontitis on type 2 diabetes: a bioinformatic analysis

Xindi Wei; Xiaomeng Zhang; Ruiying Chen; Yuan Li; Yijie Yang; Ke Deng; Zhengzhen Cai; Hongchang Lai; Junyu Shi

doi:10.1186/s12903-024-04408-1

BMC Oral Health (May 2024)

Impact of periodontitis on type 2 diabetes: a bioinformatic analysis

Xindi Wei,
Xiaomeng Zhang,
Ruiying Chen,
Yuan Li,
Yijie Yang,
Ke Deng,
Zhengzhen Cai,
Hongchang Lai,
Junyu Shi

Affiliations

Xindi Wei: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Xiaomeng Zhang: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Ruiying Chen: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Yuan Li: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Yijie Yang: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Ke Deng: Division of Periodontology and Implant Dentistry, The Faulty of Dentistry, The University of Hong Kong
Zhengzhen Cai: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Hongchang Lai: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology
Junyu Shi: Department of Oral and Maxillofacial Implantology, Shanghai PerioImplant Innovation Center, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology

DOI: https://doi.org/10.1186/s12903-024-04408-1
Journal volume & issue: Vol. 24, no. 1
pp. 1 – 11

Abstract

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Abstract Background Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. Methods A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. Results Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117–1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001–1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849–13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). Conclusions This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.

Published in BMC Oral Health

ISSN: 1472-6831 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Dentistry
Website: http://bmcoralhealth.biomedcentral.com

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