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.

【摘要 背景】神经肽Y（neuropeptide Y, NPY）是神经系统中含量最丰富的神经递质之一。NPY可通过神经肽Y2受体（NPY2R）作为血管生成、炎症反应及脂肪生成的强效刺激因子。NPY信号通路的异常改变与急性冠状动脉综合征（ACS）密切相关。
【研究目的】本研究旨在探讨NPY及NPY2R基因的变异与急性冠状动脉综合征（ACS）严重程度之间的关联。
【研究方法】本研究共纳入221名ACS患者与278名健康对照个体。采用Taqman等位基因鉴别法及测序技术对NPY基因的4个变异位点与NPY2R基因的2个变异位点进行基因分型。采用卡方检验及Fisher确切概率法验证基因型频率分布，采用logistic回归分析对研究变量进行评估，并通过单体型分析评估变异位点间的连锁不平衡（LD）关系，检验水准设定为p<0.05。
【研究结果】与健康对照组相比，NPY基因c.20T>C变异与ACS发病存在显著关联。在ACS患者亚组的变异与危险因素关联分析中，NPY基因c.84G>A变异与高血压存在关联。针对TIMI风险分层的分析显示，NPY基因c.20T>C变异在低风险组与中/高风险组间存在显著差异。单体型分析结果显示，NPY基因c.150G>A与c.-485T>C两个变异位点间存在强连锁不平衡关系。
【研究结论】NPY基因c.20T>C变异可能参与ACS的发病过程。NPY2R基因c.-1116A>G变异可能与ACS的早期发病相关，而NPY基因c.84G>A变异可能参与高血压的发生发展。此外，NPY基因c.20T>C变异对ACS的严重程度具有保护作用。