O polimorfismo AGT*M235T na disfunção cardíaca de etiologia isquêmica aguda: projeto gisca

FUNDAMENTO: O polimorfismo AGT*M235T tem sido associado a elevados níveis séricos de angiotensinogênio (AGT), hipertensão arterial sistêmica e disfunção cardíaca (DC). OBJETIVO: Testar a hipótese de haver associação entre polimorfismo AGT*M235T e o risco de desenvolver disfunção cardíaca (insuficiência cardíaca ou disfunção sistólica ventricular esquerda assintomática) pós-síndrome coronariana aguda (SCA), durante o período de internação hospitalar. MÉTODOS: Foram estudados 363 pacientes (idade média 62 ± 12 anos), sendo 233 (64%) homens e 130 (36%) mulheres, todos da mesma coorte, internados por SCA. Compararam-se dados clínicos e genéticos dos 117 (32,2%) que evoluíram com disfunção cardíaca (grupo caso) com os dos 246 (67,8%), que não desenvolveram tal condição (grupo controle). O polimorfismo AGT*M235T foi determinado por análise de sequenciamento e estava em equilíbrio de Hardy-Weinberg. RESULTADOS: Houve diferença significativa na distribuição dos genótipos nas mulheres, com predomínio do genótipo *235MM no grupo controle (p = 0,001) e do alelo *235T no grupo caso. Em ambos os sexos, nos modelos de regressão logística, o diagnóstico de infarto de parede anterior na admissão foi fator de incremento no risco de DC, enquanto angina instável na admissão, ausência do alelo *235T, glicemia < 100 mg/dl, uso de betabloqueador, creatinina sérica < 1,5 mg/dl, faixa de frequência cardíaca > 60 e < 90 bpm e tabagismo atual foram fatores de redução do risco de DC. CONCLUSÃO: Este estudo sugere que a ausência do alelo *235T do AGT contribui para a redução do risco de disfunção cardíaca pós-síndrome coronariana aguda.

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes

Background: End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes. Objective: To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis. Methods: Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study. Results: The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor. Conclusions: The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.

Análise combinada de fatores genéticos e ambientais na hipertensão essencial em um município da região Amazônica

OBJETIVO: Este estudo avaliou a contribuição de seis polimorfismos genéticos presentes em genes do sistema renina-angiotensina-aldosterona (SRAA) e fatores de risco clínicos para o desenvolvimento da hipertensão arterial essencial em um município da região Amazônica. MÉTODOS: Oitenta e dois indivíduos hipertensos e setenta e oito indivíduos normotensos foram genotipados quanto à presença de polimorfismos REN-G1051A (renina), AGT-M235T (angiotensinogênio), ECA-Alu I/D (enzima conversora de angiotensina I), AGTR1-A1166C (receptor tipo 1 da angiotensina II) e CYP11B2-C344T (aldosterona sintetase) pela técnica de reação em cadeia da polimerase (PCR), com análise de restrição quando necessário. A influência de polimorfismos genéticos e fatores de risco clínicos na variação da pressão arterial foi avaliada por meio de regressão linear stepwise. RESULTADOS: Relatamos a co-ocorrência de fatores de risco clínicos e polimorfismo do gene da enzima conversora de angiotensina (ECA) na população de um município da região amazônica. Nossos resultados mostram que a elevação da pressão arterial sistólica é favorecida pelo alelo D do polimorfismo de inserção/deleção do gene da ECA e pelo aumento da idade, enquanto consumo de bebida alcoólica e envelhecimento estão associados ao aumento da pressão arterial diastólica (PAD). CONCLUSÃO: Esses achados indicam que os moradores de Santa Isabel do Rio Negro que possuem o alelo D da ECA ou têm o hábito de beber apresentam valores mais elevados de PAS e PAD, respectivamente, com o passar dos anos.

Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension

Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.