Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis
| العنوان: | Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis |
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| المؤلفون: | Stefan Schreiber, Gesa M. Richter, Birte Groessner-Schreiber, Bruno G. Loos, Barbara Noack, Arne S. Schaefer, Michael Nothnagel, Nour-Eddine El Mokhtari, Søren Jepsen |
| المساهمون: | Parodontologie (OUD, ACTA) |
| المصدر: | PLoS Genetics, Vol 5, Iss 2, p e1000378 (2009) PLoS Genetics Schaefer, A S, Richter, G M, Groessner-Schreiber, B, Noack, D, Nothnagel, M, El Mokhtari, N E, Loos, B G, Jepsen, S & Schreiber, S 2009, ' Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis ', PLoS Genetics, vol. 5, pp. 1-8 . https://doi.org/10.1371/journal.pgen.1000378Test PLOS Genetics, 5, 1-8. Public Library of Science PLoS Genetics, 5, 1-8. Public Library of Science PLoS Genetics, 5 (2). |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Cancer Research, Linkage disequilibrium, Coronary Disease, Genome-wide association study, Bioinformatics, Linkage Disequilibrium, 0302 clinical medicine, Germany, Aggressive periodontitis, Genetics and Genomics/Genetics of Disease, Genetics (clinical), Genetics and Genomics/Medical Genetics, Genetics, 0303 health sciences, Middle Aged, 3. Good health, Female, Genetics and Genomics/Gene Discovery, Genetics and Genomics/Genetics of the Immune System, Chromosomes, Human, Pair 9, Research Article, Adult, Genotype, lcsh:QH426-470, Single-nucleotide polymorphism, Locus (genetics), Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, RNA, Antisense, Periodontitis, Molecular Biology, Cyclin-Dependent Kinase Inhibitor p16, Ecology, Evolution, Behavior and Systematics, Aged, Cyclin-Dependent Kinase Inhibitor p15, 030304 developmental biology, Haplotype, 030206 dentistry, medicine.disease, lcsh:Genetics, Diabetes Mellitus, Type 2, Immunology/Genetics of the Immune System |
| الوصف: | Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with 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 = 6.9×10−4) for generalized aggressive periodontitis, and 1.72 (1.06–2.76; P = 2.6×10−2) 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. Author Summary Coronary heart disease (CHD) and periodontitis are the most widespread diseases in the Western industrialized world and pose a substantial health threat to populations worldwide. CHD is a leading cause for premature death, and periodontitis is the major cause for tooth loss in adults over 40 years. Both diseases are associated with similar risk factors such as smoking, diabetes, and gender, and both diseases are further characterized by a chronic inflammatory process. In the last year, several genome studies have identified a region of the human genome near the CDKN2A and CDKN2B genes as having an influence on CHD. We show that this genetic region, being the most important susceptibility locus for CHD to date, is also associated with a substantial risk increase of aggressive periodontitis. The associated genetic region maps to a genomic region that codes for an “antisense RNA,” which partly overlaps regulatory and coding sequences of genes CDKN2A/CDKN2B. The interplay between these common inflammatory complex diseases could be partially due to the shared genetic risk variants of this antisense RNA. |
| وصف الملف: | application/pdf; text |
| تدمد: | 1553-7390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c835cdcefdfa557b8157dda1551be8f6Test https://hdl.handle.net/11245/1.314037Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c835cdcefdfa557b8157dda1551be8f6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537390 |
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