Influence of Neuropeptide Y and Neuropeptide Y 2 Receptor Variants in Acute Coronary Syndrome

Abstract Background The neuropeptide Y (NPY) is one of the most abundant neurotransmitters in the nervous system. NPY acts as a potent stimulator of angiogenesis, inflammation, and adipogenesis, through the NPY 2 receptor (NPY2R). Changes in the NPY signaling pathway have been linked to Acute Coronary Syndrome (ACS). Objectives The purpose of this study is to determine the association between variants in the NPY and NPY2R genes, as well as the severity of acute coronary syndrome (ACS). Methods Approximately 221 ACS patients and 278 healthy controls were selected for this study. Four variants in NPY and two variants in NPY2R genes were genotyped using Taqman allelic discrimination and sequencing. The Chi-square and Fisher's exact tests were used to verify the genotype frequencies. The logistic regression analyses were used for the evaluation of the studied variables. Haplotype analysis was used to evaluate the linkage disequilibrium (LD) between the variants (p<0.05). Results An association of NPY c.20T>C variant was found with the ACS group when compared to the healthy group. In the analysis between variants and risk factors in the ACS group, NPY c.84G>A was associated with hypertension. The analysis between TIMI risk showed a significance for NPY c.20T>C between the low and intermediate/high TIMI risk groups. In the haplotype analysis, strong linkage disequilibrium (LD) was found between the variants NPY c.150G>A and NPY c.-485T>C. Conclusion The NPY c.20T>C variant appears to contribute to the development of ACS. The NPY2R c.-1116A>G variant may contribute to the early development of ACS and the NPY c.84G>A variant appears to contribute to the development of hypertension. In addition, the NPY c.20T>C is associated with a protective effect in ACS severity.

Evaluation of Polymorphisms in IL8 and IL16 Genes in Patients with Acute Coronary Syndrome

Abstract Background: Acute coronary syndrome (ACS) is a cardiovascular disease caused by obstruction of coronary arteries by atheromatous plaque. Susceptibility to this disease may be related to genetic variations, such as single nucleotide polymorphisms (SNPs). Objective: In this study, we evaluated the relationship between SNPs in IL8 (rs4073; -251 A/T) and IL16 (rs11556218; T/G) genes and SCA in a Brazilian population. Materials and Methods: A sample of 200 patients with ACS and 50 non-ACS patients hospitalized at the Real Hospital Português, Recife - PE, Brazil, and 220 blood donors (donors) was used. Genotyping was carried out by polymerase chain reaction, and DNA sequencing. Statistical analyzes were performed using the Williams G, Chi-square and Kruskal Wallis tests, using the BioEstat 5.0 program, and the data with a value of p < 0.05 were considered significant. Results: In the IL8 gene, the AT genotype was the most frequent (p > 0.05) in all three groups. In the IL16 gene, genotypic distributions were different between patients with ACS and the donor group (p = 0.002), with the most frequent G allele in the second group (p = 0.0052). The IL-16 cytokine was higher in donors than in patients with ACS (p = 0.04) and the G (TG + GG) allele had higher values of this cytokine (p = 0.01). Conclusions: The results demonstrate the important role of the rs11556218 SNP in IL16 gene in SCA, evidencing that the G allele may be associated with a decreased risk of the disease.

Avaliação do Polimorfismo -174 G/C do gene IL-6 na Síndrome Coronariana Aguda no Nordeste do Brasil / Evaluation of IL-6 (-174 G/C) Polymorphism in Acute Coronary Syndrome in the Northeast of Brazil

Fundamento: A síndrome coronariana aguda (SCA) é a principal causa de morbidade e mortalidade no mundo. É uma doença multifatorial causada por obstrução das artérias coronárias por placa ateromatosa que leva à isquemia cardíaca. Diversos estudos sugerem que alguns polimorfismos genéticos alteram os níveis de citocinas e influenciam o desenvolvimento de SCA. Objetivo: Neste estudo, avaliamos o polimorfismo - 174 G/C do gene IL-6 , níveis séricos de citocina e sua relação com SCA e escore de risco de thrombolysis in myocardial infarction (TIMI). Materiais e métodos: Foram selecionados 200 pacientes com SCA [risco de TIMI ­ Baixo (70), Intermediário (89), Alto (41)] na população brasileira. A genotipagem foi feita pela reação em cadeia da polimerase (PCR), seguida de sequenciamento de DNA. Resultados: Não houve diferenças significativas na distribuição dos genótipos (p = 0,53) e dos alelos (p = 0,32) entre grupos de pacientes com SCA e sem SCA no polimorfismo alélico do IL-6 , nem entre os três escores de risco TIMI (p > 0,05). Além disso, o polimorfismo do IL-6 não afetou os níveis de citocina, os quais não estavam relacionados ao escore de TIMI. Conclusões: Com esses resultados, sugerimos que o polimorfismo ­ 174 G/C do gene IL-6, até agora, não está relacionado à SCA e não alterou os níveis de citocina na população estudada. Novos estudos em populações diferentes devem ser feitos para verificar esses resultados. É importante enfatizar que, como a SCA é uma doença multifatorial, outros fatores de risco e outras citocinas pró-inflamatórias devem ser avaliadas para o conhecimento dessa patologia

Background: Acute coronary syndrome (ACS) is a leading cause of morbidity and mortality worldwide. It is a multifactorial disease caused by obstruction of the coronary arteries by atheromatous plaques and leads to heart ischemia. Several studies suggest that some genetic polymorphisms change the cytokines levels and influence ACS development. Objective: In this study, we evaluated the IL-6 polymorphism -174 G/C, serum levels of cytokine and its relationship with ACS and the thrombolysis in myocardial infarction (TIMI) risk score. Materials and Methods: A sample of 200 patients with ACS [TIMI risk ­ Low (70); Intermediate (89); High (41)] in Brazilian population was used. Genotyping was carried out by polymerase chain reaction, followed by DNA sequencing. Results: There was no significant differences in genotype (p = 0.53) and allele (p = 0.32) distributions between ACS patient and without ACS patients groups on IL-6 allelic polymorphism and between the three different TIMI risk score (p > 0.05). Moreover IL-6 polymorphism did not affect the cytokine levels and these levels were not related to the TIMI score. Conclusions: With these results, we suggest that the IL-6 (-174 G/C) polymorphism, until now, is not related to ACS and did not change the levels of the cytokine in studied population. Further studies with different populations should be done to verify those results. It is important to emphasize that, since ACS is a multifactorial disease, other risk factors and other pro-inflammatory cytokines should be assessed to better understand this pathology

Comparação do perfil clínico-epidemiológico entre homens e mulheres na síndrome coronariana aguda / Comparison of clinical and epidemiological profiles among men and women with acute coronary syndrome

Fundamentos: A doença isquêmica do coração é a principal causa de morte entre homens e mulheres no Brasil e em vários países de diferentes continentes. Verifica-se um crescimento acelerado da mortalidade nos países em desenvolvimento, sendo esta considerada uma das questões mais relevantes em saúde pública atualmente. Objetivo: Analisar e comparar o perfil clínico-epidemiológico de homens e mulheres na síndrome coronariana aguda.Métodos: Avaliado o perfil clínico-epidemiológico de 927 pacientes (60,0% homens), com média de idade 67,0±12,0 anos com diagnóstico de síndrome coronariana aguda (SCA), internados na unidade coronariana de um hospital da rede suplementar de saúde, de referência em cardiologia, na cidade de Recife, PE, Brasil, no período de setembro de 2009 a dezembro de 2012.Resultados: Dentre os fatores de risco, a hipertensão arterial sistêmica e o sedentarismo foram mais frequentes nas mulheres (p=0,001), enquanto o tabagismo e o alcoolismo foram mais frequentes nos homens (p=0,01). Ainda nos homens foram mais frequentes: o infarto agudo do miocárdio com supradesnivelamento do segmento do ST ou cirurgia de revascularização do miocárdio prévios (p=0,011) e também os níveis de troponina (p=0,006). Durante a hospitalização, os desfechos adversos e óbito foram mais frequentes nas mulheres (p=0,177).Conclusão: As mulheres com SCA apresentaram maior prevalência de hipertensão arterial sistêmica e sedentarismo e a maior ocorrência de desfechos adversos, indicando a necessidade de intervir mais precocemente e estimular o controle nos fatores de risco, visando a reduzir as complicações e a mortalidade hospitalar.

Background: Ischemic heart disease is the leading cause of death among men and women in Brazil and in several countries on different continents. A sharp upsurge in mortality rates has been noted in the developing countries, today constituting a major public health issue.Objective: To analyze and compare the clinical and epidemiological profiles of men and women with acute coronary syndrome.Methods: We studied 927 patients (60.0% men) with an average age of 67.0±12.0 years diagnosed with acute coronary syndrome (ACS) and admitted to the coronary unit of a cardiology reference hospital in the supplementary healthcare network between September 2009 and December 2012 in the city of Recife, Pernambuco State, Brazil.Results: Among the risk factors, hypertension and sedentary lifestyles were more frequent among women (p=0.001), while smoking and alcoholism were more frequent among men (p=0.01). Men also had more frequent acute myocardial infarctions with elevation of the ST segment or previous coronary artery bypass grafting (p=0.011) and higher troponin levels (p=0.006). During hospitalization, adverse outcomes and deaths were more frequent among women (p=0.177).Conclusion: Women with ACS present higher rates for hypertension and sedentary lifestyles, with more adverse outcomes among women underscoring the need for earlier intervention and encouragement for controlling risk factors, in order to lower in-hospital mortality rates with fewer complications.