Genetic polymorphism of the renin-angiotensin-aldosterone system and arterial hypertension in the Italian population: The GENIPER Project
| Autor: | Federica Rossi, Nicola Glorioso, M. Giacchè, Massimo Volpe, Riccardo Sarzani, Maurizio Castellano, Gian Paolo Rossi, Giuseppe Opocher, Franco Mantero, Cristina Barlassina, R. Golin, Carmine Zoccali, Daniele Cusi, Laura Tizzoni, Fabiana Filigheddu, Franco Veglio, Bruno Fabris, Francesco Fallo |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Male
Aldosterone synthase medicine.medical_specialty Angiotensin receptor Genetic polymorphism Hypertension Renin-angiotensin system Genotype Physiology Biology Gene Frequency Risk Factors Internal medicine Databases Genetic Renin–angiotensin system Internal Medicine medicine Humans Genetic Predisposition to Disease Allele Allele frequency Polymorphism Genetic Angiotensin II receptor type 1 Middle Aged Endocrinology Blood pressure Italy biology.protein Female Cardiology and Cardiovascular Medicine |
| Popis: | Objective To detect the association of single polymorphisms of the renin-angiotensin-aldosterone system (RAAS), or different combinations thereof, with hypertension. Design and methods The GENIPER database is the result of a collaborative effort of 13 Italian research centres to collect genomic DNA in subjects well characterized in terms of blood pressure status. A total of 2461 subjects (normotensive = 611; hypertensive = 1850) were selected and genotyped for the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) T/ C 704 , angiotensin receptor type 1 (AT1) A/C 1166 and aldosterone synthase (ALDO) T/C -344 genetic variants. Results Allele frequencies were homogeneous over the Italian territory, with the relevant exception of the ACE I/D, the D allele being significantly less frequent in the northern region (61%) than in the rest of the country (67%; P < 0.0001). When comparing allele and genotype distributions in normotensives and hypertensives, the latter presented a small but statistically significant increase of the C allele of AGT T/C 704 , the A allele of AT1 A/C 1166 and the T allele of ALDO T/C -344 polymorphisms (P = 0.018, P = 0.037 and P = 0.015, respectively), with similar trends all over the country. A step-wise logistic regression analysis confirmed these findings, by entering in the model as independent predictors of blood pressure status of AGT T/C 704 (P = 0.013), ALDO T/C -344 (P = 0.032) and AT1 A/C 1166 polymorphisms (P= 0.075), but not ACE I/D (P= 0.996). We also found some evidence of an additive effect of individual genetic variants of the RAAS, modulating at different levels the same functional pathway, on the risk of developing hypertension, but no synergistic interaction was observed. Conclusions Our results suggest that some allelic variants of RAAS genes carry a small but identifiable risk of developing arterial hypertension. |
| Databáze: | OpenAIRE |
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