Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

Abstract

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10−05, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10−05, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10−05, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10−05, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10−05, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10−02, p = 5.1 × 10−03, p = 1.2 × 10−02, respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.

Identification of Neuropeptides as Potential Crosstalks Linking Down Syndrome and Periodontitis Revealed by Transcriptomic Analyses

“…This is the first bioinformatics study, which investigated the potential crosstalk between DS and periodontitis. A genetic crosstalk between periodontitis and DS has been repeatedly discussed in literature [ 8 – 10 , 15 , 16 ]. This has been evaluated in the current study, whereby the hypothesis of a potential crosstalk between these two diseases was confirmed.…”

“…This has been evaluated in the current study, whereby the hypothesis of a potential crosstalk between these two diseases was confirmed. Thereby, a recent case-control study identified single nucleotide polymorphisms (SNP) to be significantly associated to periodontal disease in DS individuals, underlining the relevance of shared genetic mechanisms [ 15 ]. It has also been found in that clinical study that different metabolic pathways, including the PI3K-Akt signaling pathway, would play an important role in this context [ 15 ].…”

“…Thereby, a recent case-control study identified single nucleotide polymorphisms (SNP) to be significantly associated to periodontal disease in DS individuals, underlining the relevance of shared genetic mechanisms [ 15 ]. It has also been found in that clinical study that different metabolic pathways, including the PI3K-Akt signaling pathway, would play an important role in this context [ 15 ]. This was also a result of the current study, where crosstalk gene TP53 and interacting neuropeptides IGF2 and INS were related to the PI3K-Akt signaling pathway.…”

“…Few previous studies revealed genes, which were differentially expressed in patients with DS in the case of periodontitis [ 8 – 10 , 15 ]. Within these studies, none out of the four crosstalk genes revealed in the current study (CD19, FCRL5, FCRLA, and HLA-DOB) was found, too.…”

“…Within these studies, none out of the four crosstalk genes revealed in the current study (CD19, FCRL5, FCRLA, and HLA-DOB) was found, too. However, while three studies only examined selected genes, excluding the crosstalk genes from the current study [ 8 – 10 ], the other available study examined salivary samples [ 15 ], making the comparability with the current study questionable. Nonetheless, there is a certain plausibility for the clinical relevance of the detected crosstalk genes in the current study.…”