The Role of Rare CARD15 Gene Variants in Aggressive Periodontitis

Background: Since similar pathogenic mechanisms may be involved in both Crohn's disease (CD) and periodontitis, a common genetic background may be inferred. However, in recent studies we and others could not show any association between the three most common CD-associated CARD15 gene variants and periodontitis. Objective: The study aimed to find additional variants in the CARD15 gene that are associated with generalized aggressive periodontitis(gAgP). Methods: 50 gAgP patients and 50 periodontally healthy controls were included in the first part of the study to search for DNA variants in exon 4 to exon 11 of the CARD15 gene. Subsequently, we examined the CARD15 genotype for 8 detected variants in 86 patients suffering from generalized AgP compared to 53 controls. Results: In addition to the three main CD-associated CARD15 gene variants, 19 different sequence variants have been identified in the first part of the study. Eight variants have known influence on NF-κB pathway or are non-conservative missense mutations. These variants were considered as potentially disease causing and were included in further analyses. The allele frequencies of these eight CARD15 variants were low in the gAgP as well as in the control group and not significantly different. All study subjects were further classified into carriers or non-carriers of at least one of the eight variants. No significant difference in carrier frequency was found between the gAgP and control group (29% vs. 24%, p=0.56 chi square test). Conclusion: Unlike in Crohn's disease, our results did not show an association between aggressive periodontitis and CARD15 mutations. The role of rare sequence variants remains unclear.

Financial support was provided by the ARPA Research Foundation of the German Society of Periodontology (DGP) as well as by the German Society of Dentistry (DGZMK).