Promoter polymorphisms in ACE (angiotensin I-converting enzyme) associated with clinical outcomes in hypertension.
Clin Pharmacol Ther
; 85(1): 36-44, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18946466
ABSTRACT
Genetic variants of ACE are suspected risk factors in cardiovascular disease, but the alleles responsible for the variations remain unidentified. To search for regulatory polymorphisms, allelic angiotensin I-converting enzyme (ACE) mRNA expression was measured in 65 heart tissues, followed by genotype scanning of the ACE locus. Marked allelic expression imbalance (AEI) detected in five African-American subjects was associated with single-nucleotide polymorphisms (SNPs) (rs7213516, rs7214530, and rs4290) residing in conserved regions 2-3 kb upstream of ACE. Moreover, each of the SNPs affected transcription in reporter gene assays. SNPs rs4290 and rs7213516 were tested for associations with adverse cardiovascular outcomes in hypertensive patients with coronary disease (International Verapamil SR Trandolapril Study Genetic Substudy (INVEST-GENES), n = 1,032). Both SNPs were associated with adverse cardiovascular outcomes, largely attributable to nonfatal myocardial infarction in African Americans, showing an odds ratio of 6.16 (2.43-15.60) (P < 0.0001) for rs7213516. The high allele frequency in African Americans (16%) compared to Hispanics (4%) and Caucasians (<1%) suggests that these alleles contribute to variation between populations in cardiovascular risk and treatment outcomes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
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Variação Genética
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Negro ou Afro-Americano
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RNA Mensageiro
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Genes Reporter
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Peptidil Dipeptidase A
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Polimorfismo de Nucleotídeo Único
/
Hipertensão
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
/
Female
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Humans
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Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos