Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort

BackgroundThe human chromosomal region 9p21.3 has been shown to be strongly associated with Coronary Heart Disease (CHD) in several Genome-wide Association Studies (GWAS). Recently, this region has also been shown to be associated with Aggressive Periodontitis (AgP), strengthening the hypothesis that the established epidemiological association between periodontitis and CHD is caused by a shared genetic background, in addition to common environmental and behavioural risk factors. However, the size of the analyzed cohorts in this primary analysis was small compared to other association studies on complex diseases. Using our own AgP cohort, we attempted to confirm the described associations for the chromosomal region 9p21.3.MethodsWe analyzed our cohort consisting of patients suffering from the most severe form of AgP, generalized AgP (gAgP) (n = 130) and appropriate periodontally healthy control individuals (n = 339) by genotyping four tagging SNPs (rs2891168, rs1333042, rs1333048 and rs496892), located in the chromosomal region 9p21.3, that have been associated with AgP.ResultsThe results confirmed significant associations between three of the four SNPs and gAgP. The combination of our results with those from the study which described this association for the first time in a meta-analysis of the four tagging SNPs produced clearly lower p-values compared with the results of each individual study. According to these results, the most plausible genetic model for the association of all four tested SNPs with gAgP seems to be the multiplicative one.ConclusionWe positively replicated the finding of an association between the chromosomal region 9p21.3 and gAgP. This result strengthens support for the hypothesis that shared susceptibility genes within this chromosomal locus might be involved in the pathogenesis of both CHD and gAgP.

[1]  W. Ketterl.  [Periodontal diseases]. , 1971, Der Zahnarzt; Colloquium med. dent.

[2]  K. Hiller,et al.  Reasons for tooth extraction in the western states of Germany. , 1993, Community dentistry and oral epidemiology.

[3]  L. Berkman,et al.  Genetic susceptibility to death from coronary heart disease in a study of twins. , 1994, The New England journal of medicine.

[4]  J. Yarnell.  The PRIME study: classical risk factors do not explain the severalfold differences in risk of coronary heart disease between France and Northern Ireland. Prospective Epidemiological Study of Myocardial Infarction. , 1998, QJM : monthly journal of the Association of Physicians.

[5]  D. Graves,et al.  IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. , 1998, Journal of immunology.

[6]  R. Kaplan,et al.  Systemic inflammation as a cardiovascular disease risk factor and as a potential target for drug therapy. , 2001, Heart disease.

[7]  U. John,et al.  Study of Health in Pomerania (SHIP): a health survey in an East German region. Objectives and design of the oral health section. , 2003, Quintessence international.

[8]  Thomas E Van Dyke,et al.  Cardiovascular disease and periodontal diseases: commonality and causation. , 2004, Compendium of continuing education in dentistry.

[9]  David M Bohnenkamp,et al.  The use of sectional impressions and a transfer index for extensive fixed prosthodontic treatment. , 2004, Compendium of continuing education in dentistry.

[10]  M. Laine,et al.  Identification of genetic risk factors for periodontitis and possible mechanisms of action. , 2005, Journal of clinical periodontology.

[11]  U. John,et al.  Study of Health in Pomerania (SHIP): A health examination survey in an east German region: Objectives and design , 2005, Sozial- und Präventivmedizin.

[12]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[13]  Alan D. Lopez,et al.  Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data , 2006, The Lancet.

[14]  H. Meng,et al.  Determinants of host susceptibility in aggressive periodontitis. , 2007, Periodontology 2000.

[15]  C. Gieger,et al.  Genomewide association analysis of coronary artery disease. , 2007, The New England journal of medicine.

[16]  Sarabjeet Singh,et al.  The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis. , 2007, American heart journal.

[17]  A Common Allele on Chromosome 9 Associated with Coronary Heart Disease , 2007, Science.

[18]  Simon C. Potter,et al.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls , 2007, Nature.

[19]  Yi Wang,et al.  BMC Medical Genetics , 2007 .

[20]  A. Gylfason,et al.  A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction , 2007, Science.

[21]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[22]  A. Evans,et al.  Persistently raised C-reactive protein levels are associated with advanced periodontal disease. , 2008, Journal of clinical periodontology.

[23]  Ludwig A Hothorn,et al.  Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9 p 21 . 3 and Coronary Artery Disease , 2008 .

[24]  G. R. Persson,et al.  Cardiovascular disease and periodontitis: an update on the associations and risk. , 2008, Journal of clinical periodontology.

[25]  B. Größner-Schreiber,et al.  Polymorphisms in the interleukin-1 (IL1) gene cluster are not associated with aggressive periodontitis in a large Caucasian population. , 2008, Genomics.

[26]  Karen L. Mohlke,et al.  INK4/ARF Transcript Expression Is Associated with Chromosome 9p21 Variants Linked to Atherosclerosis , 2009, PloS one.

[27]  J. Parker,et al.  Functional Analysis of the Chromosome 9p21.3 Coronary Artery Disease Risk Locus , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[28]  Bruno G. Loos,et al.  UvA-DARE ( Digital Academic Repository ) Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis , 2009 .