Background: The receptor of advanced glycation end products (RAGE) is mediating inflammatory processes e.g. involved in the occurrence of severe periodontitis via activation of transcription factor NF-B. Its expression is influenced by the c.-374T>A-SNP, located in the promoter region of this gene. The aim of this study was to evaluate links between this SNP and the occurrence of aggressive periodontitis. Patients and Methods: 81 patients with generalized aggressive periodontitis (mean age: 40.4+9.8y, 63% females) and 85 periodontitisfree controls (mean age: 46.7+10.8y, 54.1% females) were included in the study. The c.-374T>A-SNP was determined by RFLP using Tsp509I restriction endonuclease. Clinical parameters including smoking status, plaque and bleeding indexes, pocket depth and attachment loss were assessed. Subgingival bacterial colonization was evaluated molecularbiologically using the micro-Ident®test (Hain Diagnostik, Nehren). Results: Investigating genotype and allele frequencies of the c.-374T>a SNP, it could be shown that carrier of the AT+TT genotypes (pcorr.=0.003, OR=14.4, 95%CI: 1.84-113.2) as well as T-allele carriers (pcorr.=0.026, OR=1.8, 95%CI: 1.1-2.8) are at higher risk for aggressive periodontitis. In binary logistic regression analysis, the T-allel (OR=1.8, 95%CI: 1.07-2.97, p=0.026) could be proven as an independent risk factor for aggressive periodontitis considering age, gender, smoking, and clinical attachment loss as confounding factors. No genotype or allele dependent associations with clinical markers of periodontitis including the subgingival occurrence of periodontopathogens could be proven for this SNP. Conclusions: The results emphasize the role of the T-allele of RAGE-SNP c.-374T>A as a putative risk indicator for aggressive periodontitis in this German cohort irrespective of further periodontal risk factors. This finding could be possibly based on an impaired immune response due to the decreased promoter activity associated with the T-allele. Keywords: periodontitis, polymorhisms, RAGE-gene