IADR Abstract Archives
Tobacco Smoking Interacts with Genetic Variants to Cause Aggressive Periodontitis
Objectives: Aggressive periodontitis (AgP) is a disease of complex etiology in which smoking and the genetic susceptibility play important roles. Even though the contributions of smoking and the genetic predisposition are well established inidividual risk factors of AgP, the interactions between genetic variants and smoking in modifying disease susceptibility are not studied systematically.
Methods: To identify specific gene x smoking interactions (G×S), we anaylsed 79,780,573 common genetic variants in 669 European AgP patients using imputed genotypes of the OmniExpress BeadChip. We compared never vs. ever smokers in a logistic regression analysis using a case-only approach. To explore those genes further, where statistically significant interactions with smoking were identified, primary gingival fibroblasts of healthy donors (pGF; N = 9) were exposed to cigarette smoke extract (CSE) and changes in transcript levels of the G×S associated pGF-expressed protein-coding genes were analyzed by quantitative reverse transcription PCR.
Results: We identified 16 loci for which the G×S interaction analysis suggested association with AgP (P < 5×10-5), nine of which were previously reported to be associated with smoking related traits. Of these, genome-wide significant cis-expression quantitiative trait loci (eQTLs) were reported for the associations at ST8SIA1 and SOST. Exposure of CSE to pGF cells significantly altered the expression of the associated genes SSH1 (P = 5 x 10-07) and ST8SIA1 (P = 0.0048). These four genes have documented functions in osteoclast regulation and tissue repair.
Conclusions: The genetic predisposition to early-onset forms of periodontitis is in parts triggered by smoking, and cigarette smoke directly affects the expression of genes involved in bone homeostasis and tissue repair. The presented data help to explain why some individuals suffer an increased early-onset disease risk if they smoke cigarettes. Our study contributes to defining risk groups and improves our understanding of the pathopyhioloy of periodontitis as a result of the interaction of life-style and environmental factors with the individual genetic predisposition.
Methods: To identify specific gene x smoking interactions (G×S), we anaylsed 79,780,573 common genetic variants in 669 European AgP patients using imputed genotypes of the OmniExpress BeadChip. We compared never vs. ever smokers in a logistic regression analysis using a case-only approach. To explore those genes further, where statistically significant interactions with smoking were identified, primary gingival fibroblasts of healthy donors (pGF; N = 9) were exposed to cigarette smoke extract (CSE) and changes in transcript levels of the G×S associated pGF-expressed protein-coding genes were analyzed by quantitative reverse transcription PCR.
Results: We identified 16 loci for which the G×S interaction analysis suggested association with AgP (P < 5×10-5), nine of which were previously reported to be associated with smoking related traits. Of these, genome-wide significant cis-expression quantitiative trait loci (eQTLs) were reported for the associations at ST8SIA1 and SOST. Exposure of CSE to pGF cells significantly altered the expression of the associated genes SSH1 (P = 5 x 10-07) and ST8SIA1 (P = 0.0048). These four genes have documented functions in osteoclast regulation and tissue repair.
Conclusions: The genetic predisposition to early-onset forms of periodontitis is in parts triggered by smoking, and cigarette smoke directly affects the expression of genes involved in bone homeostasis and tissue repair. The presented data help to explain why some individuals suffer an increased early-onset disease risk if they smoke cigarettes. Our study contributes to defining risk groups and improves our understanding of the pathopyhioloy of periodontitis as a result of the interaction of life-style and environmental factors with the individual genetic predisposition.