Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women

In worldwide studies, interleukin-6 (IL-6) is implicated in age-related disturbances. The aim of the present report was to determine the possible association of IL-6 -174 C/G promoter polymorphism with the cytokine profile as well as with the presence of selected cardiovascular risk features. This was a cross-sectional study on Brazilian women aged 60 years or older. A sample of 193 subjects was investigated for impaired glucose regulation, diabetes, hypertension, and dyslipidemia. Genotyping was done by direct sequencing of PCR products. IL-6 and C-reactive protein were quantified by high-sensitivity assays. General linear regression models or the Student t-test were used to compare continuous variables among genotypes, followed by adjustments for confounding variables. The chi-square test was used to compare categorical variables. The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In a recessive model, mean waist-to-hip ratio, serum glycated hemoglobin and serum glucose were markedly lower in C homozygotes (P = 0.001, 0.028, and 0.047, respectively). In a dominant hypothesis, G homozygotes displayed a trend towards higher levels of circulating IL-6 (P = 0.092). Non-parametric analysis revealed that impaired fasting glucose and hypertension were findings approximately 2-fold more frequent among G homozygous subjects (P = 0.042 and 0.043, respectively). Taken together, our results show that the IL-6 -174 G-allele is implicated in a greater cardiovascular risk. To our knowledge, this is the first investigation of IL-6 promoter variants and age-related disturbances in the Brazilian elderly population

Investigação de associação entre estimativas de ancestralidade genômica e evolução clínica após infarto agudo do miocárdio : Brasília Heart study

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências Médicas, Programa de Pós-Graduação em Ciências Médicas, 2015.As doenças cardiovasculares (DCV) constituem a principal causa de morte nos países desenvolvidos e em desenvolvimento. Destaca-se o infarto agudo do miocárdio (IAM) como causa isolada responsável pela maior proporção de mortes por etiologia orgânica em homens e mulheres. A participação dos fatores de risco clássicos (tabagismo, sedentarismo, dislipidemias, hipertensão e outros) para o desenvolvimento do IAM encontra-se bem descrita na literatura. Entretanto, a contribuição da herança genética advinda de distintos grupos populacionais humanos (a exemplo do europeu, do africano sub-saariano e do ameríndio) para a manifestação fenotípica e a evolução clínica do IAM ainda é pouco mensurada. O presente estudo investigou a associação de estimativas de ancestralidade genômica, determinada por marcadores informativos de ancestralidade (AIMs), com variáveis clínicas e bioquímicas representativas de risco de recidiva ou de complicações no período pós-infarto em amostra da população brasileira, que se caracteriza em sua formação por um importante grau de ancestralidade tri-híbrida. As estimativas de ancestralidade [europeia (EUR), africana (AFR) e ameríndia (AMR)] foram determinadas pela genotipagem de 18 AIMs em 408 pacientes admitidos no Brasília Heart Study (BHS) com diagnóstico de IAM com supradesnivelamento do segmento ST. Variáveis bioquímicas (perfil lipídico, glicêmico e outras) foram medidas nas primeiras 24 horas pós-evento. Variáveis clínicas (antropométricas, pressóricas, gravidade de Killip-Kimbal e marcadores de lesão miocárdica) foram determinadas no quinto dia de hospitalização. A proporção média de ascendência individual determinada na amostra foi de (EUR = 70,4%), (AFR = 24,3%) e (AMR = 5,2%). Testes de correlações revelaram associação negativa entre níveis de ancestralidade AMR e as variáveis pressóricas [sistólica (P = 0,021); diastólica (P = 0,018)] e com a frequência cardíaca [FC; (P = 0,006)]. Regressões lineares confirmaram esses achados. Dicotomização da amostra entre portadores ou não de determinada ancestralidade confirmou, por aplicação do teste t de Student, valores médios aumentados das variáveis pressóricas [sistólica (P = 0,006); diastólica (P = 0,005); FC (P = 0,005)] entre sujeitos não-AMR. Observou-se também uma associação positiva ao analisar os valores médios aferidos para a variável PAD (P = 0.028) e uma tendência à significância estatística para a PAS (P = 0.056), entre indivíduos com ancestralidade EUR . Ademais, pela análise do qui-quadrado, houve maior frequência de história familiar de doença arterial coronariana entre portadores de ancestralidade AFR (P = 0,024) assim como maior proporção de uso de betabloqueadores entre sujeitos com ancestralidade EUR (P =0,020). Pelo conjunto exposto, nossos resultados sugerem que maior proporção genômica ameríndia no indivíduo pode conferir proteção ao fenótipo da hipertensão arterial sistêmica no curso clínico do pós-IAM.Cardiovascular diseases (CVD) are the leading cause of death in developed and developing countries. The highest proportion of deaths from organic etiology in men and women is caused by acute myocardial infarction (AMI). The contribution of the classical risk factors (smoking, physical inactivity, dyslipidemia, hypertension and others) to the development of AMI are well described in literature. However, the contribution of genetic heritage of different human population groups (such as the European, the sub-Saharan African and Amerindian) for phenotypic expression and the clinical evolution of AMI is still poorly measured. This study investigated the association of genetic ancestry, determined by ancestry informative markers (AIMs), with representative clinical and biochemical variables of risk of recurrence or complications in the post-infarction in a sample of the Brazilian population, which is characterized in their formation a material degree of ancestry tri-hybrid. Estimates of ancestry [European (EUR), African (AFR) and Native American (AMR)] were determined by genotyping 18 AIMs in 408 patients admitted to the Brazilian Heart Study (BHS) diagnosed with acute myocardial infarction with ST-segment elevation. Biochemical variables (lipid and glucose profiles, and others) were measured within the first 24 hours after the event. Clinical variables (anthropometric, blood pressure, Killip-Kimball classification and myocardial injury markers) were determined on the fifth day of hospitalization. The average ratio of individual ancestry at the sample was EUR = 70.4%, AFR = 24.3% and AMR = 5.2%. Correlation tests revealed negative association between levels of AMR ancestry and blood pressure [systolic (P = 0.021); diastolic (P = 0.018)] and heart rate [HR; (P = 0.006)] variables. Linear regressions confirmed these findings. Dichotomization of the sample between patients with or without a given ancestry confirmed increased mean values of the blood pressure variables [systolic (P = 0.006); diastolic (P = 0.005); FC (P = 0.005)] between subjects with non-AMR ancestry.It was also observed a positive association to analyze the mean values measured for the variable PAD (P = 0.028) and a trend towards statistical significance for SBP (P = 0.056) between individuals with EUR ancestry. Furthermore, the chi-square analysis showed that there was a higher frequency of family history of coronary artery disease among patients with ancestry AFR (P = 0.024) as well as a higher proportion of beta-blockers among individuals with ancestry EUR (P = 0.020). Based on the above considerations, our results suggest that a greater Amerindian proportion in the subject can provide protection to the phenotype of hypertension in the post-AMI clinical setting

Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α.

Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ]) in response to multivariate drug directions for blood pressure (BP) control. Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention. Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P0.01) at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group. Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in reversing the low-grade proinflammatory state of serum cytokines found in post¬menopausal women and support extracardiac benefits from diuretics and renin–angiotensin system antagonist

Circulating Interleukin-6 (but Not Other Immune Mediators) Associates with Criteria for Fried’s Frailty among Very Old Adults

Background and Aim. Frailty is a geriatric condition resulting from physiological changes covering the musculoskeletal, immune, and neuroendocrine systems, leading to a greater inflammatory state. The present research aimed to investigate the association of components of Fried’s frailty (as well as of the phenotype as a whole) with total serum levels of a panel of inflammatory mediators. Methods. One hundred and sixty-one very old patients (aged ≥80 years) devoid of cognitive decline were eligible for analyses. Clinical and biochemical data along with physical and cognitive assessments encompassing dual-energy X-ray scans and hand dynamometry were adopted to investigate frailty criteria, while circulating immune mediators (IFNγ, IL-2, IL-4, IL-6, IL-10, and TNFα) were assessed using high-throughput flow cytometry. Results. Preliminarily, IL-6 correlated positively with waist-to-hip ratio and C-reactive protein and negatively with glycemia. In analyses controlled for these factors, serum levels of IL-6 were comparatively augmented among the very old participants with reduced grip strength (OR = 3.299; 95% CI 1.08–6.09; p=0.032) and among those with slow walk speed (OR = 2.460; 95% CI 1.16–7.05; p=0.022). Conclusions. Our study shows a strong negative correlation of IL-6 levels with Fried’s frailty components of grip strength and walk speed in very old adults, regardless of confounding factors

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer

Metalloproteinases (MMPs) are involved in metastatic tumor processes, with changes in circulating levels detected in several cancer types. Here, we compare serum concentrations of metalloproteinase-1 (MMP-1) across individuals clinically diagnosed with prostate cancer (PCa) or benign prostatic hyperplasia (BPH), correcting results for the rs495366 single nucleotide polymorphism (SNP) that predisposes to differential MMP-1 levels. 196 men aged ≥50 years were followed at a university hospital urology outpatient clinic, with clinical, anthropometric, and rectal examinations performed by one urologist. Blood samples obtained prior to any clinical intervention provided baseline MMP-1 and total/free PSA levels as well as metabolic, hormonal, and inflammatory markers. The SNP was genotyped by real-time PCR. Participants with medical and/or laboratory profile compatible with malignancy composed the PCa group when confirmed by the Gleason scale. As expected, A-allele homozygotes showed reduced levels of MMP-1. Genotype-adjusted analyses revealed the mean MMP-1 level as 2-fold higher in PCa carriers compared to BPH patients. No other differences were found according to the prostatic condition or genotypic distribution, except for the expected raise in total and free PSA levels in PCa. In conclusion, increased serum levels of MMP-1 were observed in this context of prostatic malignancy compared to a benign phenotype, regardless of a genetic influence