背景:有证据表明Notch1信号通路有助于手的发育,脚,和口蹄疫(HFMD);然而,Notch1基因多态性在柯萨奇病毒A6(CVA6)相关HFMD严重程度中的作用尚不清楚.本研究旨在探讨Notch1基因多态性与CVA6相关性手足口病严重程度的相关性。
方法:共196例经核酸检测确诊为CVA6相关性手足口病的患者(中国汉族人群)纳入本研究。其中,97例患者被归类为重症病例,而99例被归类为轻度。采用实时定量聚合酶链反应(qRT-PCR)检测HFMD患者外周血白细胞中Notch1的mRNA水平,并利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对rs3124599,rs3124603和rs3124591进行基因分型。
结果:rs3124599等位基因频率为G(39.0%)和A(61.0%),而rs3124599基因型的频率为GG(12.2%),GA(53.6%),和AA(34.2%),分别。在隐性模型中,rs3124599AA基因型的频率在重症患者中显著增加,与轻度患者相比(P<0.05)。由于rs3124591和rs3124603在患者中的等位基因频率较低,以及两组之间的分布没有任何差异(P>0.05),没有进行额外的统计学分析.在调整了年龄和性别后,与G等位基因携带者(GA/GG)相比,rs3124599AA基因型的患者患重症手足口病的风险明显更高,比值比(95%置信区间)为2.010(1.094,3.691)。同时,与轻度患者相比,重度患者中Notch1的mRNA水平显着升高(P<0.05),Notch1mRNA水平与外周血单核细胞计数呈正相关(r=0.42,P<0.001)。此外,AA基因型rs3124599患者的Notch1mRNA水平和外周血单核细胞计数与GA基因型或G等位基因携带者之间存在显着差异(P<0.05)。
结论:在中国汉族人群中,Notch1rs3124599等位基因与CVA6相关HFMD的严重程度之间存在很强的相关性。这种相关性可能归因于调节Notch1转录水平的rs3124599的遗传多态性。这些发现揭示了Notch1基因多态性在CVA6感染中的重要作用。为精准控制重症手足口病奠定科学基础。
BACKGROUND: There is evidence suggesting that
Notch1 signaling pathway contributes to the development of hand, foot, and mouth disease (HFMD); however, the role of
Notch1 gene polymorphisms in the severity of coxsackievirus A6 (CVA6)-related HFMD remains unclear. This study aimed to investigate the correlation between
Notch1 gene polymorphisms and the severity of CVA6-related HFMD.
METHODS: A total of 196 patients (Chinese Han population) diagnosed with CVA6-related HFMD through nucleic acid testing were included in this study. Among them, 97 patients were classified as severe cases, while 99 cases were categorized as mild. The mRNA levels of Notch1 in the peripheral blood leukocytes of HFMD patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was utilized for genotyping of rs3124599, rs3124603, and rs3124591.
RESULTS: The frequencies of rs3124599 alleles were G (39.0%) and A (61.0%), while the frequencies of rs3124599 genotypes were GG (12.2%), GA (53.6%), and AA (34.2%), respectively. In the recessive model, the frequency of rs3124599 AA genotypes significantly increased in severe patients, compared to mild patients (P < 0.05). Due to the low frequency of alleles for rs3124591 and rs3124603 in patients, as well as the absence of any difference in their distribution between the two groups (P > 0.05), no additional statistical analysis was performed. After adjusting for age and sex, patients with rs3124599 AA genotype had a significantly higher risk of severe HFMD in comparison to G allele carriers (GA/GG), with an odds ratio (95% confidence interval) of 2.010 (1.094, 3.691). Meanwhile, the mRNA levels of Notch1 were found to be significantly higher in severe patients compared to mild patients (P < 0.05), and a positive correlation was observed between
Notch1 mRNA levels and the peripheral blood monocyte count (r = 0.42, P < 0.001). Additionally, there were significant differences observed in
Notch1 mRNA levels and peripheral blood monocyte counts between patients with the AA genotype of rs3124599 and those with the GA genotype or G allele carriers (P < 0.05).
CONCLUSIONS: In the Chinese Han population, there is a strong correlation between the Notch1 rs3124599 allele and the severity of CVA6-related HFMD. This correlation may be attributed to genetic polymorphism of rs3124599 regulating Notch1 transcription levels. These findings reveal the important role of Notch1 gene polymorphism in CVA6 infection, establishing a scientific foundation for the precise control of severe HFMD.