Genotype impacts survival in Marfan syndrome
| Autor: | Gerard Pals, Janneke Timmermans, Arthur J.H.A. Scholte, Maarten P. van den Berg, Romy Franken, Barbara J.M. Mulder, Maarten Groenink, Helena M. A. Feenstra, Vivian de Waard, Aeilko H. Zwinderman |
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| Přispěvatelé: | Cardiology, Radiology and Nuclear Medicine, Medical Biochemistry, Epidemiology and Data Science, Cardiovascular Centre (CVC), Surgery, RS: FHML non-thematic output, Human genetics, ICaR - Ischemia and repair |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Marfan syndrome Adult Male EXPRESSION medicine.medical_specialty Genotype Survival Fibrillin-1 Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] PATHOGENESIS Aortic dissection 030204 cardiovascular system & hematology 030105 genetics & heredity Fibrillins Gastroenterology DISEASE 03 medical and health sciences Aortic aneurysm 0302 clinical medicine FBN1 GENE medicine.artery Internal medicine medicine Humans Risk factor MUTATION Aorta FBN1 mutation business.industry Hazard ratio Microfilament Proteins medicine.disease Surgery CLINICAL PHENOTYPES Female LOSARTAN Cardiology and Cardiovascular Medicine Complication Haploinsufficiency business |
| Zdroj: | European heart journal, 37(43), 3285-3290. Oxford University Press European Heart Journal, 37, 43, pp. 3285-3290 Franken, R, Groenink, M, de Waard, V, Feenstra, H M A, Scholte, A J, van den Berg, M P, Pals, G, Zwinderman, A H, Timmermans, J & Mulder, B J M 2016, ' Genotype impacts survival in Marfan syndrome ', European Heart Journal, vol. 37, no. 43, pp. 3285-3290 . https://doi.org/10.1093/eurheartj/ehv739 European Heart Journal, 37(43), 3285-3290. Oxford University Press European Heart Journal, 37(43). Oxford University Press European Heart Journal, 37, 3285-3290 European Heart Journal, 36, 523-523 |
| ISSN: | 0195-668X |
| Popis: | Item does not contain fulltext AIMS: The aorta in Marfan syndrome (MFS) patients is variably affected. We investigated the assumed genotype-effect on protein production as a risk factor for a severe aortic phenotype in adult MFS patients. METHODS AND RESULTS: We collected clinical and genetic data from all 570 adults with MFS who had been included in the Dutch CONgenital CORvitia registry since the start in 2001. Mean age was 36.5 +/- 13.5 years (51.2% male, 28.9% prior aortic surgery, 8.2% prior aortic dissection). Patients were prospectively followed for a mean duration of 8.2 +/- 3.1 years. Men had more frequently aortic surgery at baseline (38.0 vs. 19.4%, P < 0.001) and during follow-up (24.0 vs. 15.1%, P = 0.008) compared with women. After 10-year follow-up cumulative survival was 93.8% and dissection-free survival was 84.2%. We found a pathogenic FBN1 mutation in 357 patients, of whom 146 patients (40.9%) were positive for a mutation causing haploinsufficiency (reduced fibrillin-1 protein) and 211 (59.1%) for a mutation leading to a DN effect (abnormal fibrillin-1 protein). Corrected for age, sex, and previous aortic complications, patients with a haploinsufficient (HI) mutation had a 2.5-fold increased risk for cardiovascular death (hazard ratio, HR: 2.5, 95% CI: 1.0-6.1, P = 0.049), a 2.4-fold increased risk for the combined endpoint comprising death and dissection (HR: 2.4, 95% CI: 1.4-4.2, P < 0.001) and a 1.6-fold increased risk for any aortic complication compared with patients with a DN mutation (HR: 1.6, 95% CI 1.1-2.3, P = 0.014). CONCLUSION: Marfan syndrome patients with an HI mutation are at increased risk for cardiovascular death and aortic dissection compared with patients with a DN mutation. |
| Databáze: | OpenAIRE |
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