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• W2113011485 abstract "Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, <i>CDKN2BAS</i> was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of <i>CDKN2BAS</i> including the adjacent genes <i>CDKN2A</i> and <i>CDKN2B</i>, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of <i>CDKN2BAS, CDKN2A, CDKN2B</i>, and <i>CDK4</i> in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of <i>CDKN2BAS</i> in healthy CT compared to GE (p=0.004). After 24 h of stimulation with <i>Porphyromonas gingivalis</i> in <i>Streptococcus gordonii</i> pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of <i>CDKN2BAS</i> gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of <i>CDKN2BAS</i> in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD." @default.
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• W2113011485 date "2010-10-26" @default.
• W2113011485 modified "2023-10-16" @default.
• W2113011485 title "CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection" @default.
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• W2113011485 doi "https://doi.org/10.1136/jmg.2010.078998" @default.
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• W2113011485 hasPublicationYear "2010" @default.
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