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Innovaci\u00f3n Biosanitaria del Principado de Asturias (FINBA)","award":["SEC\/FEC-INV-BAS22\/014"],"award-info":[{"award-number":["SEC\/FEC-INV-BAS22\/014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cellular communication network factor 2 (CCN2\/CTGF) has been traditionally described as a downstream mediator of other profibrotic factors including transforming growth factor (TGF)-\u03b2 and angiotensin II. However, recent evidence from our group demonstrated the direct role of CCN2 in maintaining aortic wall homeostasis and acute and lethal aortic aneurysm development induced by angiotensin II in the absence of CCN2 in mice. In order to translate these findings to humans, we evaluated the potential association between three polymorphisms in the CCN2 gene and the presence of a thoracic aortic aneurysm (TAA). Patients with and without TAA retrospectively selected were genotyped for rs6918698, rs9402373 and rs12526196 polymorphisms related to the CCN2 gene. Multivariable logistic regression models were performed. In our population of 366 patients (69 with TAA), no associations were found between rs6918698 and rs9402373 and TAA. However, the presence of one C allele from rs12526196 was associated with TAA comparing with the TT genotype, independently of risk factors such as sex, age, hypertension, type of valvulopathy and the presence of a bicuspid aortic valve (OR = 3.17; 95% CI = 1.30\u20137.88; p = 0.011). In conclusion, we demonstrated an association between the C allele of rs12526196 in the CCN2 gene and the presence of TAA. This study extrapolates to humans the relevance of CCN2 in aortic aneurysm observed in mice and postulates, for the first time, a potential protective role to CCN2 in aortic aneurysm pathology. Our results encourage future research to explore new variants in the CCN2 gene that could be predisposed to TAA development.<\/jats:p>","DOI":"10.3390\/ijms232315406","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T01:47:46Z","timestamp":1670377666000},"page":"15406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The CCN2 Polymorphism rs12526196 Is a Risk Factor for Ascending Thoracic Aortic Aneurysm"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7954-5753","authenticated-orcid":false,"given":"Antonio","family":"Tejera-Mu\u00f1oz","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology in Renal and Vascular Pathology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"},{"name":"Research Support Unit, Hospital General Mancha Centro, 13600 Alc\u00e1zar de San Juan, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-1411","authenticated-orcid":false,"given":"Isabel","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Cardiac Pathology Research Group, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6048-958X","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Del R\u00edo-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Cardiac Pathology Research Group, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamina","family":"Mohamedi","sequence":"additional","affiliation":[{"name":"Cardiac Pathology Research Group, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Cardiac Pathology Research Group, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"},{"name":"Cardiology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Chiminazzo","sequence":"additional","affiliation":[{"name":"Biostatistics and Epidemiology Platform, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Su\u00e1rez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Translational Immunology, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias ISPA, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"L\u00f3pez-Larrea","sequence":"additional","affiliation":[{"name":"Translational Immunology, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias ISPA, 33011 Oviedo, Spain"},{"name":"Servicio de Inmunolog\u00eda, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-6535","authenticated-orcid":false,"given":"Marta","family":"Ruiz-Ortega","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology in Renal and Vascular Pathology, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Universidad Aut\u00f3noma de Madrid, Av Reyes Cat\u00f3licos 2, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-6709","authenticated-orcid":false,"given":"Ra\u00fal R.","family":"Rodrigues-D\u00edez","sequence":"additional","affiliation":[{"name":"Translational Immunology, Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias ISPA, 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1242\/jcs.03270","article-title":"All in the CCN family: Essential matricellular signaling modulators emerge from the bunker","volume":"119","author":"Leask","year":"2006","journal-title":"J. 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