Aggressive periodontitis and NOD2 variants

• Published in: Journal of human genetics Vol. 65; no. 10; pp. 841 - 846
• Main Authors: Mizuno, Noriyoshi, Kume, Kodai, Nagatani, Yukiko, Matsuda, Shinji, Iwata, Tomoyuki, Ouhara, Kazuhisa, Kajiya, Mikihito, Takeda, Katsuhiro, Matsuda, Yukiko, Tada, Yui, Ohsawa, Ryosuke, Morino, Hiroyuki, Mihara, Keichiro, Fujita, Tsuyoshi, Kawaguchi, Hiroyuki, Shiba, Hideki, Kawakami, Hideshi, Kurihara, Hidemi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2020
• Subjects: Adult; Aggressive Periodontitis - diagnostic imaging; Aggressive Periodontitis - genetics; Aggressive Periodontitis - immunology; Caspase; Crohn's disease; Female; Genetic Predisposition to Disease; Gum disease; Heterozygote; Humans; Immune response; Leucine; Leukocytes; Male; Mutation, Missense; NOD2 protein; Nod2 Signaling Adaptor Protein - chemistry; Nod2 Signaling Adaptor Protein - genetics; Oligomerization; Pedigree; Periodontitis; Peripheral blood; Protein Domains; Proteins
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/s10038-020-0777-z

Aggressive periodontitis (AgP) occurs at an early age and causes rapid periodontal tissue destruction. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) encodes a protein with two caspase recruitment domains and eleven leucine-rich repeats. This protein is expressed mainly in peripheral blood leukocytes and is involved in immune response. NOD2 variants have been associated with increased susceptibility to Crohn's disease, and recently, NOD2 was reported as a causative gene in AgP. The present study aimed to identify potential NOD2 variants in an AgP cohort (a total of 101 patiens: 37 patients with positive family histories and 64 sporadic patients). In the familial group, six patients from two families had a reported heterozygous missense variant (c.C931T, p.R311W). Four patients in the sporadic group had a heterozygous missense variant (c.C1411T, p.R471C), with no reported association to the disease. Overall, two NOD2 variants, were identified in 10% of our AgP cohort. These variants were different from the major variants reported in Crohn's disease. More cases need to be investigated to elucidate the role of NOD2 variants in AgP pathology.