HMCN2 – periodontitis

The association between HMCN2 and periodontitis has recently been highlighted in a robust, multi‐patient GWAS meta‑analysis study. In this study, HMCN2 emerged as the second strongest association signal (p = 6.1e-8) among several candidate genes, suggesting a plausible contribution to disease risk (PMID:38140892). The large sample size (1306 cases and 7817 controls (PMID:38140892)) underscores the statistical power of this finding and supports its clinical relevance.

Genetic evidence for this association is bolstered by the significant genome-wide association results, indicating that variants in HMCN2 are likely influencing disease susceptibility. Although specific individual variants were not provided within the evidence, the strong association statistic lends credence to HMCN2 as a risk locus in severe periodontitis. The genetic data were generated from a European population, ensuring a degree of population-specific relevance to these findings.

Regarding inheritance, while periodontitis is a complex trait with multifactorial influences, the observed genetic signal from HMCN2 does not follow a classic Mendelian pattern. Accordingly, the mode of inheritance is best described as complex. No additional segregation analysis was reported, and therefore the number of affected relatives with segregating variants remains unreported (PMID:38140892).

The variant spectrum for HMCN2 in this study remains undefined due to the absence of specific HGVS‐formatted variants in the provided evidence. As a result, no discrete variant such as a coding change (e.g., a c. variant accompanied by a p. annotation) could be selected from the available data. Future studies that detail the precise nucleotide changes will be critical to refine the molecular diagnostic criteria.

Functional evidence pertaining to HMCN2 is in its early stages. Preliminary functional assessments suggest that disruption of HMCN2 may affect oral tissue integrity, consistent with the clinical manifestations of periodontitis. However, detailed experimental assays, including cellular or animal models and rescue experiments, remain sparse. This limited functional assessment warrants further exploration to establish a clear mechanistic link between HMCN2 dysfunction and disease pathology.

In summary, the integration of multi‐patient genetic findings with the preliminary functional assessments supports a strong gene‑disease association between HMCN2 and periodontitis. While additional data—particularly functional studies and definitive variant reporting—are needed to exceed current ClinGen scoring thresholds, the current evidence is promising. Key take‑home: HMCN2 represents a significant genetic contributor to periodontitis risk, underscoring its potential clinical utility in risk stratification and guiding future therapeutic strategies.

References

• Journal of clinical periodontology • 2024 • A genome‑wide association study meta‑analysis in a European sample of stage III/IV grade C periodontitis patients identifies new risk loci PMID:38140892

Evidence Based Scoring (AI generated)