Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans.
alveolar bone loss
gene × sex interaction
genetic risk
heritability
inflammation
Journal
Journal of clinical periodontology
ISSN: 1600-051X
Titre abrégé: J Clin Periodontol
Pays: United States
ID NLM: 0425123
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
29
06
2021
accepted:
03
07
2021
pubmed:
20
8
2021
medline:
1
12
2021
entrez:
19
8
2021
Statut:
ppublish
Résumé
Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.
Substances chimiques
CPEB4 protein, human
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1404-1413Informations de copyright
© 2021 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.
Références
Aulchenko, Y. S., Struchalin, M. V., & van Duijn, C. M. (2010). ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics, 11, 134. https://doi.org/10.1186/1471-2105-11-134
Buniello, A., MacArthur, J. A. L., Cerezo, M., Harris, L. W., Hayhurst, J., Malangone, C., McMahon, A., Morales, J., Mountjoy, E., Sollis, E., Suveges, D., Vrousgou, O., Whetzel, P. L., Amode, R., Guillen, J. A., Riat, H. S., Trevanion, S. J., Hall, P., Junkins, H., … Parkinson, H. (2019). The NHGRI-EBI GWAS catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Research, 47(D1), D1005-D1012. https://doi.org/10.1093/nar/gky1120
Camus, M. F., Piper, M. D., & Reuter, M. (2019). Sex-specific transcriptomic responses to changes in the nutritional environment. eLife, 8, e47262. https://doi.org/10.7554/eLife.47262
Cauley, J. A. (2011). Defining ethnic and racial differences in osteoporosis and fragility fractures. Clinical Orthopaedics and Related Research, 469(7), 1891-1899. https://doi.org/10.1007/s11999-011-1863-5
Divaris, K., Monda, K. L., North, K. E., Olshan, A. F., Reynolds, L. M., Hsueh, W. C., Lange, E. M., Moss, K., Barros, S. P., Weyant, R. J., Liu, Y., Newman, A. B., Beck, J. D., & Offenbacher, S. (2013). Exploring the genetic basis of chronic periodontitis: A genome-wide association study. Human Molecular Genetics, 22, 2312-2324. https://doi.org/10.1093/hmg/ddt065
Freitag-Wolf, S., Dommisch, H., Graetz, C., Jockel-Schneider, Y., Harks, I., Staufenbiel, I., Meyle, J., Eickholz, P., Noack, B., Bruckmann, C., Gieger, C., Jepsen, S., Lieb, W., Schreiber, S., König, I. R., & Schaefer, A. S. (2014). Genome-wide exploration identifies sex-specific genetic effects of alleles upstream NPY to increase the risk of severe periodontitis in men. Journal of Clinical Periodontology, 41(12), 1115-1121. https://doi.org/10.1111/jcpe.12317
Freitag-Wolf, S., Munz, M., Wiehe, R., Junge, O., Graetz, C., Jockel-Schneider, Y., Staufenbiel, I., Bruckmann, C., Lieb, W., Franke, A., Loos, B. G., Jepsen, S., Dommisch, H., & Schaefer, A. S. (2019). Smoking modifies the genetic risk for early-onset periodontitis. Journal of Dental Research, 98(12), 1332-1339. https://doi.org/10.1177/0022034519875443
Hormand, J., & Frandsen, A. (1979). Juvenile periodontitis. Localization of bone loss in relation to age, sex, and teeth. Journal of Clinical Periodontology, 6(6), 407-416. https://doi.org/10.1111/j.1600-051x.1979.tb01939.x
Hu, S., Shang, W., Yue, H., Chen, R., Dong, Z., Hu, J., Mao, Z., & Yang, J. (2015). Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis. Archives of Oral Biology, 60(4), 517-525. https://doi.org/10.1016/j.archoralbio.2014.12.006
Kebschull, M., Demmer, R. T., Grun, B., Guarnieri, P., Pavlidis, P., & Papapanou, P. N. (2014). Gingival tissue transcriptomes identify distinct periodontitis phenotypes. Journal of Dental Research, 93(5), 459-468. https://doi.org/10.1177/0022034514527288
Kim, J. S., Ryoo, Z. Y., & Chun, J. S. (2007). Cytokine-like 1 (Cytl1) regulates the chondrogenesis of mesenchymal cells. The Journal of Biological Chemistry, 282(40), 29359-29367. https://doi.org/10.1074/jbc.M700965200
Levin, L., Baev, V., Lev, R., Stabholz, A., & Ashkenazi, M. (2006). Aggressive periodontitis among young Israeli army personnel. Journal of Periodontology, 77(8), 1392-1396. https://doi.org/10.1902/jop.2006.050323
Loe, H., & Brown, L. J. (1991). Early onset periodontitis in The United States of America. Journal of Periodontology, 62(10), 608-616. https://doi.org/10.1902/jop.1991.62.10.608
Meisel, P., Eremenko, M., Holtfreter, B., Volzke, H., & Kocher, T. (2019). The sex paradox in the interplay between periodontitis, obesity, and serum C-reactive protein: Data from a general population. Journal of Periodontology, 90(12), 1365-1373. https://doi.org/10.1002/JPER.18-0733
Melvin, W. L., Sandifer, J. B., & Gray, J. L. (1991). The prevalence and sex ratio of juvenile periodontitis in a young racially mixed population. Journal of Periodontology, 62(5), 330-334. https://doi.org/10.1902/jop.1991.62.5.330
Mondragon-Ceballos, R., Garcia Granados, M. D., Cerda-Molina, A. L., Chavira-Ramirez, R., & Hernandez-Lopez, L. E. (2015). Waist-to-hip ratio, but not body mass index, is associated with testosterone and estradiol concentrations in young women. International Journal of Endocrinology, 2015, 654046. https://doi.org/10.1155/2015/654046
Monteferrario, D., Bolar, N. A., Marneth, A. E., Hebeda, K. M., Bergevoet, S. M., Veenstra, H., Laros-van Gorkom, B. A., MacKenzie, M. A., Khandanpour, C., Botezatu, L., & Fransen, E. (2014). A dominant-negative GFI1B mutation in the gray platelet syndrome. The New England Journal of Medicine, 370(3), 245-253. https://doi.org/10.1056/NEJMoa1308130
Munz, M., Richter, G. M., Loos, B. G., Jepsen, S., Divaris, K., Offenbacher, S., Teumer, A., Holtfreter, B., Kocher, T., Bruckmann, C., Jockel-Schneider, Y., Graetz, C., Ahmad, I., Staufenbiel, I., van der Velde, N., Uitterlinden, A. G., de Groot, L. C. P. G. M., Wellmann, J., Berger, K., … Schaefer, A. S. (2019). Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci. European Journal of Human Genetics, 27(1), 102-113. https://doi.org/10.1038/s41431-018-0265-5
Munz, M., Willenborg, C., Richter, G. M., Jockel-Schneider, Y., Graetz, C., Staufenbiel, I., Wellmann, J., Berger, K., Krone, B., Hoffmann, P., van der Velde, N., Uitterlinden, A. G., de Groot, L. C. P. G. M., Sawalha, A. H., Direskeneli, H., Saruhan-Direskeneli, G., Guzeldemir-Akcakanat, E., Keceli, H. G., Laudes, M., … Schaefer, A. S. (2017). A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis. Human Molecular Genetics, 26, 2577-2588. https://doi.org/10.1093/hmg/ddx151
Munz, M., Wohlers, I., Simon, E., Reinberger, T., Busch, H., Schaefer, A. S., & Erdmann, J. (2020). Qtlizer: Comprehensive QTL annotation of GWAS results. Scientific Reports, 10(1), 20417. https://doi.org/10.1038/s41598-020-75770-7
Ober, C., Loisel, D. A., & Gilad, Y. (2008). Sex-specific genetic architecture of human disease. Nature Reviews. Genetics, 9(12), 911-922. https://doi.org/10.1038/nrg2415
Ortiz-Zapater, E., Pineda, D., Martinez-Bosch, N., Fernandez-Miranda, G., Iglesias, M., Alameda, F., Moreno, M., Eliscovich, C., Eyras, E., Real, F. X., & Méndez, R. (2011). Key contribution of CPEB4-mediated translational control to cancer progression. Nature Medicine, 18(1), 83-90. https://doi.org/10.1038/nm.2540
Piegorsch, W. W., Weinberg, C. R., & Taylor, J. A. (1994). Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies. Statistics in Medicine, 13(2), 153-162.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., Maller, J., Sklar, P., De Bakker, P. I., Daly, M. J., & Sham, P. C. (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 81(3), 559-575.
Sanders, A. E., Sofer, T., Wong, Q., Kerr, K. F., Agler, C., Shaffer, J. R., Beck, J. D., Offenbacher, S., Salazar, C. R., North, K. E., Marazita, M. L., Laurie, C. C., Singer, R. H., Cai, J., Finlayson, T. L., & Divaris, K. (2017). Chronic periodontitis genome-wide association study in the Hispanic community health study/study of Latinos. Journal of Dental Research, 96(1), 64-72. https://doi.org/10.1177/0022034516664509
Saxby, M. (1984). Prevalence of juvenile periodontitis in a British school population. Community Dentistry and Oral Epidemiology, 12(3), 185-187. https://doi.org/10.1111/j.1600-0528.1984.tb01435.x
Saxby, M. S. (1987). Juvenile periodontitis: An epidemiological study in the west midlands of the United Kingdom. Journal of Clinical Periodontology, 14(10), 594-598. https://doi.org/10.1111/j.1600-051x.1987.tb01521.x
Schaefer, A. S., Bochenek, G., Jochens, A., Ellinghaus, D., Dommisch, H., Guzeldemir-Akcakanat, E., Graetz, C., Harks, I., Jockel-Schneider, Y., Weinspach, K., & Meyle, J. (2015). Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis. Circulation. Cardiovascular Genetics, 8(1), 159-167. https://doi.org/10.1161/CIRCGENETICS.114.000554
Seney, M. L., Huo, Z., Cahill, K., French, L., Puralewski, R., Zhang, J., Logan, R. W., Tseng, G., Lewis, D. A., & Sibille, E. (2018). Opposite molecular signatures of depression in men and women. Biological Psychiatry, 84(1), 18-27. https://doi.org/10.1016/j.biopsych.2018.01.017
Steffens, J. P., Valenga, H. M., Santana, L. C. L., Albaricci, M., Kantarci, A., & Spolidorio, L. C. (2019). Role of testosterone and androgen receptor in periodontal disease progression in female rats. Journal of Periodontology, 91, 545-553. https://doi.org/10.1002/JPER.19-0099
Sullivan, D. A., Jensen, R. V., Suzuki, T., & Richards, S. M. (2009). Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands? Molecular Vision, 15, 1553-1572.
Sulniute, R., Lindh, T., Wilczynska, M., Li, J., & Ny, T. (2011). Plasmin is essential in preventing periodontitis in mice. The American Journal of Pathology, 179(2), 819-828. https://doi.org/10.1016/j.ajpath.2011.05.003
Susin, C., & Albandar, J. M. (2005). Aggressive periodontitis in an urban population in southern Brazil. Journal of Periodontology, 76(3), 468-475. https://doi.org/10.1902/jop.2005.76.3.468
Teumer, A., Holtfreter, B., Volker, U., Petersmann, A., Nauck, M., Biffar, R., Völzke, H., Kroemer, H. K., Meisel, P., Homuth, G., & Kocher, T. (2013). Genome-wide association study of chronic periodontitis in a general German population. Journal of Clinical Periodontology, 40(11), 977-985. https://doi.org/10.1111/jcpe.12154
Traglia, M., Bseiso, D., Gusev, A., Adviento, B., Park, D. S., Mefford, J. A., Zaitlen, N., & Weiss, L. A. (2017). Genetic mechanisms leading to sex differences across common diseases and anthropometric traits. Genetics, 205(2), 979-992. https://doi.org/10.1534/genetics.116.193623
Weiss, L. A., Pan, L., Abney, M., & Ober, C. (2006). The sex-specific genetic architecture of quantitative traits in humans. Nature Genetics, 38(2), 218-222. https://doi.org/10.1038/ng1726
Yu, J., Yun, H., Shin, B., Kim, Y., Park, E. S., Choi, S., Yu, J., Amarasekara, D. S., Kim, S., Inoue, J. I., Walsh, M. C., Choi, Y., Takami, M., & Rho, J. (2016). Interaction of tumor necrosis factor receptor-associated factor 6 (TRAF6) and Vav3 in the receptor activator of nuclear factor kappaB (RANK) signaling complex enhances Osteoclastogenesis. The Journal of Biological Chemistry, 291(39), 20643-20660. https://doi.org/10.1074/jbc.M116.728303