Genetic Variation of Kallikrein-Kinin System and Related Genes in Patients With Hereditary Angioedema
| Autor: | Eli Mansour, Rozana Fátima Gonçalves, Anette Bygum, Agatha Ribeiro Mendes, Jane Da Silva, Mar Guilarte, Priscila Nicolicht, Camila Lopes Veronez, Rafael Filippelli-Silva, Anete Sevciovic Grumach, Renan Paulo Martin, Anne Aabom, João Bosco Pesquero |
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| Přispěvatelé: | Institut Català de la Salut, [Veronez CL, Nicholicht P, Filippelli-Silva R] Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil. [Aabom A] Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark. [Martin RP] Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil. Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, United States. [Gonçalves RF] Private Allergy and Immunology Clinic, Belo Horizonte, Brazil. [Guilarte M] Servei d'Al•lergologia, Servei de Medicina Interna, Hospital Universitari Vall d'Hebron, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2019 |
| Předmět: |
Genotype-phenotype correlation
Chemical Phenomena::Biochemical Phenomena::Osmoregulation::Water-Electrolyte Balance::Kallikrein-Kinin System [PHENOMENA AND PROCESSES] Kallikrein-Kinin System fenómenos químicos::fenómenos bioquímicos::osmorregulación::equilibrio hidroelectrolítico::sistema calicreína-cinina [FENÓMENOS Y PROCESOS] genotype-phenotype correlation Biology Genotype-phenotype distinction fenómenos genéticos::variación genética [FENÓMENOS Y PROCESOS] Genetic variation Other subheadings::Other subheadings::/genetics [Other subheadings] medicine Epigenetics Gene Hereditary angioedema Genetics F12 mutation lcsh:R5-920 Genetic diversity Otros calificadores::Otros calificadores::/genética [Otros calificadores] Mutació (Biologia) Autosomal dominant trait General Medicine Brief Research Report medicine.disease Phenotype Cardiovascular Diseases::Vascular Diseases::Angioedema::Angioedemas Hereditary [DISEASES] hereditary angioedema Edema - Aspectes genètics Genetic Phenomena::Genetic Variation [PHENOMENA AND PROCESSES] Proteïnes de la sang genetic variation Medicine C1 inhibitor deficiency lcsh:Medicine (General) enfermedades cardiovasculares::enfermedades vasculares::angioedema::angioedemas hereditarios [ENFERMEDADES] |
| Zdroj: | Frontiers in Medicine, Vol 6 (2019) Frontiers in Medicine Veronez, C L, Aabom, A, Martin, R P, Filippelli-Silva, R, Gonçalves, R F, Nicolicht, P, Mendes, A R, Da Silva, J, Guilarte, M, Grumach, A S, Mansour, E, Bygum, A & Pesquero, J B 2019, ' Genetic variation of Kallikrein-Kinin system and related genes in patients with hereditary angioedema ', Frontiers in Medicine, vol. 6, no. FEB, 28 . https://doi.org/10.3389/fmed.2019.00028 Scientia |
| ISSN: | 2296-858X |
| DOI: | 10.3389/fmed.2019.00028 |
| Popis: | Kallikrein-Kinin System; Genetic variation; Hereditary angioedema Sistema calicreina-cinina; Variació genètica; Angioedema hereditari Sistema calicreina-cinina; Variación genética; Angioedema hereditario Hereditary angioedema (HAE) is an autosomal dominant disease caused by C1-INH deficiency due to mutations in SERPING1 (C1-INH-HAE) in most of the cases, or by specific mutations in factor XII gene, F12 (F12-HAE). Identification of polymorphisms in the genes encoding proteins from key pathways driving HAE can help to understand how genetic diversity contributes to its phenotypic variability. Here, 15 genes related to the Kallikrein-Kinin System (KKS) were analyzed by next generation sequencing in 59 patients with C1-INH-HAE or F12-HAE from Brazil, Denmark and Spain, and 19 healthy relatives in a total of 31 families. We identified 211 variants, from which 23 occurred only in Danish subjects and 79 were found only in Brazilian individuals, resulting in 109/211 variations in common between European and Brazilian population in the HAE families analyzed. BDKRB2 and CPM presented a large number of variants in untranslated regions, 46/49 and 19/24, respectively; whereas ACE (n = 26), SERPING1 (n = 26), CPM (n = 24), and NOS3 (n = 16) genes presented the higher number of variants directly affecting amino acid sequence. Despite the large amount of variants identified, the lack of association between genotype and phenotype indicates that the modulation of HAE symptom requires a more complex regulation, probably involving pathways beyond the KKS, epigenetics and environmental factors. Considering the new HAE types recently described, molecules involved in the regulation of vasculature and in plasminogen activation become promising targets for future genetic studies. |
| Databáze: | OpenAIRE |
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