PADI1 – Periodontitis

Recent exome sequencing studies in families affected by severe early‑onset periodontitis have identified rare, deleterious variants in PADI1 (HGNC:18367) as potential contributors to disease risk (PMID:34515563). Although the overall number of affected individuals harboring these variants is limited, their presence in affected siblings underscores a possible role for PADI1 in disease susceptibility.

The genetic evidence is based on observations in which two affected siblings from one family carried heterozygous deleterious mutations in PADI1. This finding, along with the autosomal dominant pattern inferred from the heterozygous state, provides preliminary support for an association, though the minimal segregation data curtails stronger classification (PMID:34515563).

Complementing the genetic data, multiple functional studies have demonstrated that PADI1 expression is tightly regulated in keratinocytes. In these studies, transcription factors such as MZF1, Sp1, and NF-κB were shown to bind regulatory regions of PADI1, thereby modulating its expression in a calcium‐dependent manner (PMID:17851584) and via an intronic enhancer mechanism (PMID:20596086).

Experimental assays including promoter reporter analyses and chromatin immunoprecipitation collectively confirm that PADI1 is subject to intricate transcriptional control. These findings imply that alterations in PADI1 regulation may disturb periodontal tissue homeostasis, which is critical in the pathogenesis of periodontitis.

While the current genetic evidence is limited by the small case count and minimal familial segregation, the concordant functional studies lend moderate support to the role of PADI1 in periodontitis. The integration of both data streams suggests that, although provisional, the association of PADI1 with periodontitis is worthy of further exploration.

Key take‑home: Despite the limited genetic evidence, the supporting functional data provide a rational basis for incorporating PADI1 evaluation into the diagnostic workup of early‑onset periodontitis, offering an avenue for tailored management strategies.

References

• Journal of dental research • 2022 • Exome Sequencing of 5 Families with Severe Early‑Onset Periodontitis PMID:34515563
• The Journal of investigative dermatology • 2008 • Crucial roles of MZF1 and Sp1 in the transcriptional regulation of PADI1 in human keratinocytes PMID:17851584
• The Journal of investigative dermatology • 2010 • An intronic enhancer contributes to transcriptional regulation of PADI1 in human keratinocytes PMID:20596086

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