Presentation Time: Monday, 4:00 p.m. - 4:15 p.m.
A. Schaefer1, G. M. Richter1, B. Groessner-Schreiber2, B. Noack3, M. Nothnagel4, N. El Mokhtari5, B. G. Loos6, S. Jepsen7, S. Schreiber1;
1Institute for Clinical Molecular Biology, Kiel, Germany, 2University Medical Center Schleswig-Holstein, Campus Kiel, Department of Operative Dentistry and Periodontology, Kiel, Germany, 3University Medical Center Carl Gustav Carus der Technischen Universität Dresden, Zentrum für Zahn-, Mund- und Kieferheilkunde, Dresden, Germany, 4University Medical Center Schleswig-Holstein, Campus Kiel, Institute of Medical Informatics and Statistics, Kiel, Germany, 5University Medical Center Schleswig-Holstein, Clinic of Cardiology, Kiel, Germany, 6Departement of Periodontology, Academic Centre for Dentistry Amsterdam, Amsterdam, Netherlands, 7Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany.
Presentation Number: C10.5
Keyword: Coronary Heart Disease, Periodontitis, shared genetic susceptibility locus
Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with by similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD, and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33-2.94; P = 6.9 x 10-4) for generalized aggressive periodontitis, and 1.72 (1.06-2.76; P = 2.6 x 10-2) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases.