Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis
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...
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| Veröffentlicht in: | PLoS genetics 2009-02, Vol.5 (2), p.e1000378-e1000378 |
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| creator | Schaefer, Arne S Richter, Gesa M Groessner-Schreiber, Birte Noack, Barbara Nothnagel, Michael El Mokhtari, Nour-Eddine Loos, Bruno G Jepsen, Søren Schreiber, Stefan |
| description | 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 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. |
| doi_str_mv | 10.1371/journal.pgen.1000378 |
| format | Article |
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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 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.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1000378</identifier><identifier>PMID: 19214202</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Cardiovascular disease ; Chromosomes, Human, Pair 9 - genetics ; Confidence intervals ; Coronary Disease - genetics ; Coronary heart disease ; Cyclin-Dependent Kinase Inhibitor p15 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Female ; Genetic aspects ; Genetic Predisposition to Disease ; Genetic susceptibility ; Genetics ; Genetics and Genomics/Gene Discovery ; Genetics and Genomics/Genetics of Disease ; Genetics and Genomics/Genetics of the Immune System ; Genetics and Genomics/Medical Genetics ; Genomes ; Genotype ; Germany ; Health risk assessment ; Heart ; Humans ; Immunology/Genetics of the Immune System ; Linkage Disequilibrium ; Male ; Middle Aged ; Periodontitis ; Periodontitis - genetics ; Polymorphism, Single Nucleotide ; Risk factors ; RNA, Antisense - genetics ; Single nucleotide polymorphisms</subject><ispartof>PLoS genetics, 2009-02, Vol.5 (2), p.e1000378-e1000378</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>Schaefer et al. 2009</rights><rights>2009 Schaefer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Schaefer AS, Richter GM, Groessner-Schreiber B, Noack B, Nothnagel M, et al. (2009) Identification of a Shared Genetic Susceptibility Locus for Coronary Heart Disease and Periodontitis. 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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 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.</description><subject>Adult</subject><subject>Aged</subject><subject>Cardiovascular disease</subject><subject>Chromosomes, Human, Pair 9 - genetics</subject><subject>Confidence intervals</subject><subject>Coronary Disease - genetics</subject><subject>Coronary heart disease</subject><subject>Cyclin-Dependent Kinase Inhibitor p15 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic susceptibility</subject><subject>Genetics</subject><subject>Genetics and Genomics/Gene Discovery</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Genetics and Genomics/Genetics of the Immune System</subject><subject>Genetics and Genomics/Medical Genetics</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Germany</subject><subject>Health risk assessment</subject><subject>Heart</subject><subject>Humans</subject><subject>Immunology/Genetics of the Immune System</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Periodontitis</subject><subject>Periodontitis - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk factors</subject><subject>RNA, Antisense - genetics</subject><subject>Single nucleotide polymorphisms</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkl2PEyEUhidG466r_8AoV5t40crnMNyYbDZ-NNm4iV-3hIFDSzMdKjAb999LbdX2TsMF5PCcF3h5m-Y5wXPCJHm9jlMazTDfLmGcE4wxk92D5pwIwWaSY_7waH3WPMl5XRHRKfm4OSOKEk4xPW_cwsFYgg_WlBBHFD0yKK9MAoeqMJRgUZ6yhW0JfRhCuUdDtFNGPiZkY4qjSfdoBSYV5EIGkwGZ0aEtpBBdrNIl5KfNI2-GDM8O80Xz9d3bL9cfZje37xfXVzczKxkvM8W5971RGAMVnipnOKWUAKO4k5SLtmtdLzwoAYx3SnWqrrkRVBJpMcXsonm5190OMeuDQVkTRpggVHBRicWecNGs9TaFTb2-jiboX4WYlrq-JNgBNO561zlPbSsx7x3vfStty4jgircWXNV6czht6jfgbPUxmeFE9HRnDCu9jHeatoxK0VWBy4NAit8nyEVvQnV6GMwIccq6bRXFbccrON-DS1MvFkYfq56tw8Em2DiCD7V-RZSgrew4rQ2vThoqU-BHWZopZ734_Ok_2I__zt5-O2Uvj9iakKGschymXczyKcj3oE0x5wT-j4UE613Uf_-k3kVdH6Je214c2_-36ZBt9hMT5fqM</recordid><startdate>20090201</startdate><enddate>20090201</enddate><creator>Schaefer, Arne S</creator><creator>Richter, Gesa M</creator><creator>Groessner-Schreiber, Birte</creator><creator>Noack, Barbara</creator><creator>Nothnagel, Michael</creator><creator>El Mokhtari, Nour-Eddine</creator><creator>Loos, Bruno G</creator><creator>Jepsen, Søren</creator><creator>Schreiber, Stefan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090201</creationdate><title>Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis</title><author>Schaefer, Arne S ; Richter, Gesa M ; Groessner-Schreiber, Birte ; Noack, Barbara ; Nothnagel, Michael ; El Mokhtari, Nour-Eddine ; Loos, Bruno G ; Jepsen, Søren ; Schreiber, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c734t-944ffba900e25f29da42221e32087245686db5fe95e3489989fe94a52717c0203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Cardiovascular disease</topic><topic>Chromosomes, Human, Pair 9 - genetics</topic><topic>Confidence intervals</topic><topic>Coronary Disease - genetics</topic><topic>Coronary heart disease</topic><topic>Cyclin-Dependent Kinase Inhibitor p15 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic susceptibility</topic><topic>Genetics</topic><topic>Genetics and Genomics/Gene Discovery</topic><topic>Genetics and Genomics/Genetics of Disease</topic><topic>Genetics and Genomics/Genetics of the Immune System</topic><topic>Genetics and Genomics/Medical Genetics</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Germany</topic><topic>Health risk assessment</topic><topic>Heart</topic><topic>Humans</topic><topic>Immunology/Genetics of the Immune System</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Periodontitis</topic><topic>Periodontitis - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk factors</topic><topic>RNA, Antisense - genetics</topic><topic>Single nucleotide polymorphisms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schaefer, Arne S</creatorcontrib><creatorcontrib>Richter, Gesa M</creatorcontrib><creatorcontrib>Groessner-Schreiber, Birte</creatorcontrib><creatorcontrib>Noack, Barbara</creatorcontrib><creatorcontrib>Nothnagel, Michael</creatorcontrib><creatorcontrib>El Mokhtari, Nour-Eddine</creatorcontrib><creatorcontrib>Loos, Bruno G</creatorcontrib><creatorcontrib>Jepsen, Søren</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schaefer, Arne S</au><au>Richter, Gesa M</au><au>Groessner-Schreiber, Birte</au><au>Noack, Barbara</au><au>Nothnagel, Michael</au><au>El Mokhtari, Nour-Eddine</au><au>Loos, Bruno G</au><au>Jepsen, Søren</au><au>Schreiber, Stefan</au><au>Marchini, Jonathan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>5</volume><issue>2</issue><spage>e1000378</spage><epage>e1000378</epage><pages>e1000378-e1000378</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>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 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19214202</pmid><doi>10.1371/journal.pgen.1000378</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Cardiovascular disease Chromosomes, Human, Pair 9 - genetics Confidence intervals Coronary Disease - genetics Coronary heart disease Cyclin-Dependent Kinase Inhibitor p15 - genetics Cyclin-Dependent Kinase Inhibitor p16 - genetics Diabetes Diabetes Mellitus, Type 2 - genetics Female Genetic aspects Genetic Predisposition to Disease Genetic susceptibility Genetics Genetics and Genomics/Gene Discovery Genetics and Genomics/Genetics of Disease Genetics and Genomics/Genetics of the Immune System Genetics and Genomics/Medical Genetics Genomes Genotype Germany Health risk assessment Heart Humans Immunology/Genetics of the Immune System Linkage Disequilibrium Male Middle Aged Periodontitis Periodontitis - genetics Polymorphism, Single Nucleotide Risk factors RNA, Antisense - genetics Single nucleotide polymorphisms |
| title | Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis |
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