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The PF4/PPBP/CXCL5 Gene Cluster Is Associated with Periodontitis
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نویسنده
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shusterman a. ,munz m. ,richter g. ,jepsen s. ,lieb w. ,krone b. ,hoffman p. ,laudes m. ,wellmann j. ,berger k. ,kocher t. ,offenbacher s. ,divaris k. ,franke a. ,schreiber s. ,dommisch h. ,weiss e. ,schaefer a.s. ,houri-haddad y. ,iraqi f.a.
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منبع
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journal of dental research - 2017 - دوره : 96 - شماره : 8 - صفحه:945 -952
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چکیده
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Periodontitis is a common dysbiotic inflammatory disease with an estimated heritability of 50%. due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity,genome-wide association studies (gwas) of chronic periodontitis (cp) have been unsuccessful in discovering susceptibility factors. a strategy that combines agnostic gwas with a well-powered candidate-gene approach has the potential to discover novel loci. we combined rna-seq data from gingival tissues with quantitative trait loci (qtls) that were identified in a f2-cross of mice resistant and susceptible to infection with oral bacterial pathogens. four genes,which were located within the mapped qtls,showed differential expression. the chromosomal regions across the human orthologous were interrogated for putative periodontitis-associated variants using existing gwas data from a german case-control sample of aggressive periodontitis (agp; 651 cases,4,001 controls),the most severe and early onset form of periodontitis. two haplotype blocks,one upstream to the coding region of ugt2a1 (rs146712414,p = 9.1 × 10-'5; odds ratio [or],1.34; 95% confidence interval [ci],1.16-1.56) and one downstream of the genes pf4/ppbp/cxcl5 (rs1595009,p = 1.3 × 10-'4; or,1.32; 95% ci,1.15-1.52),were associated with agp. the association of rs1595009 was validated in an independent cohort of cp of european americans (1,961 cases and 1,864 controls; p = 0.03; or,1.45; 95% ci,1.01-1.29). this association was further replicated in another sample of 399 german cp cases (disease onset <60 y of age) and 1,633 controls (p = 0.03; or,1.75; 95% ci,1.06-2.90). the combined estimates of association from all samples were p = 2.9 × 10-'5 (or,1.2; 95% ci,1.1-1.3). this study shows the strength of combining qtl mapping and rna-seq data from a mouse model with association studies in human case-control samples to identify genetic risk variants of periodontitis. © international & american associations for dental research 2017.
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کلیدواژه
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alveolar bone loss; association; genetic; GWAS; mice model; QTL mapping
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آدرس
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department of prosthodontics,hadassah faculty of dental medicine,hebrew university,jerusalem, Israel, department of periodontology and synoptic medicine,institute for dental and craniofacial sciences,charité-university medicine berlin,berlin,germany,institute for integrative and experimental genomics,university medical center,schleswig-holstein-campus lübeck,lübeck, Germany, department of periodontology and synoptic medicine,institute for dental and craniofacial sciences,charité-university medicine berlin,berlin, Germany, department of periodontology,operative and preventive dentistry,university of bonn,bonn, Germany, institute of epidemiology,biobank popgen,christian-albrechts-university,kiel, Germany, institute of medical informatics,biometry and epidemiology,university clinic essen,essen, Germany, institute of human genetics,university of bonn,bonn,germany,germany und human genomics research group,department of biomedicine,university hospital of basel,basel, Switzerland, clinic of internal medicine,university clinic schleswig-holstein,kiel, Germany, institute of epidemiology and social medicine,university of münster,münster, Germany, institute of epidemiology and social medicine,university of münster,münster, Germany, unit of periodontology,dept. of restorative dentistry,periodontology,endodontology,preventive dentistry and pedodontics,dental school,university medicine greifswald,greifswald, Germany, university of north carolina-chapel hill,school of dentistry,department of periodontology,chapel hill,nc, United States, university of north carolina-chapel hill,school of dentistry,department of pediatric dentistry,chapel hill,nc,united states,university of north carolina-chapel hill,gillings school of global public health,department of epidemiology,chapel hill,nc, United States, institute of clinical molecular biology,christian-albrechts-university,kiel, Germany, clinic of internal medicine,university clinic schleswig-holstein,kiel,germany,institute of clinical molecular biology,christian-albrechts-university,kiel, Germany, department of periodontology and synoptic medicine,institute for dental and craniofacial sciences,charité-university medicine berlin,berlin, Germany, maurice and gabriella goldschleger school of dental medicine,sackler faculty of medicine,tel aviv university,tel aviv, Israel, department of periodontology and synoptic medicine,institute for dental and craniofacial sciences,charité-university medicine berlin,berlin, Germany, department of prosthodontics,hadassah faculty of dental medicine,hebrew university,jerusalem, Israel, department of clinical microbiology and immunology,sackler faculty of medicine,tel aviv university,tel aviv, Israel
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Authors
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