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 the influence of global DNA methylation level in patients with acute coronary syndrome.

DNA methylation is one of the mechanisms of epigenetic regulation and is observed in mammals to maintain a normal expression pattern of the genes. Aberrant profiles of DNA methylation have already been associated with cardiovascular diseases. We evaluated 190 patients with Acute Coronary Syndrome (ACS) and 75 patients without ACS (non-ACS). Patient severity was assessed by the TIMI risk score, and both levels of global DNA methylation (ACS = 190; non-ACS = 75), stratified in expected group (male ≥ 65 years; female ≥ 55 years) and early group (male < 65 years; female < 55 years). As results, the ACS and non-ACS groups showed different levels of global DNA methylation, and patients with ACS were more methylated (p = 0.0121). Patients with ACS, showed a difference (p < 0.0001) in methylation profiles between groups. The low TIMI group had a higher level of DNA methylation, while the intermediate / high group showed a decreased methylation pattern. A negative correlation was observed between the level of global methylation and the increase in age (p = 0.0387; r = -0.15), which became hypomethylated over the years. The hypermethylated global DNA profile by its association with the development of ACS can be a potential biomarker.

Discrimination of Leishmania braziliensis variants by kDNA signatures produced by LSSP-PCR.

The conventional methods for identification and typing of Leishmania species depend on previous culture isolation of the parasites. Not infrequently, culture is unsuccessful and may result in misrepresentation of the heterogeneity of the original isolate. Thus, more reliable and precise identification of genotypes of Leishmania spp. is important for a better clinical and epidemiological understanding of the disease. We evaluated the potential of LSSP-PCR targeting kDNA minicircles in discriminating different variants of the parasite with the use of clinical samples directly or cultivated parasites. The 1st step of this procedure consists of the amplification of the minicircles by conventional PCR; the 2nd step is low-stringency amplification of the minicircles previously amplified, with the use of 1 of the primers. Although LSSP-PCR produced complex and distinct kDNA signatures for isolates representing different species, further experiments demonstrated that the approach had the potential for discriminating intraspecific variants of L. braziliensis. Thus, the generated profiles were too variable to be useful as markers for species identification. Moreover, we demonstrated that the approach can be directly applied to clinical samples. In conclusion, LSSP-PCR targeting kDNA minicircles produces profiles that reflect polymorphisms of the predominant classes of minicircles, and can be useful for studies aimed at discriminating Leishmania braziliensis genotypes without the need for previous cultivation of the parasite.