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先天性巨细胞病毒感染中单核苷酸多态性与病毒载量的关系。

Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection.

机构信息

Department of Neontology and Neonatal Intensive Care , The Children's Memorial Health Institute, Warsaw, Poland.

Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Warsaw, Poland.

出版信息

J Mother Child. 2021 Jul 16;24(4):9-17. doi: 10.34763/jmotherandchild.20202404.d-20-00014.

Abstract

BACKGROUND

There are limited data on factors that determine viral load (VL) in congenital cytomegalovirus (cCMV) infection. Single nucleotide polymorphisms (SNPs) might influence individual host response to infection. This study aimed to investigate the association between SNPs in genes encoding cytokines or cytokine receptors and VL in newborns with cCMV.

MATERIAL AND METHODS

Eight polymorphisms (IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791 and TLR9 rs352140) were analyzed in study population of 233 newborns, including 92 cCMV-infected newborns (73 symptomatic and 19 asymptomatic) by TaqMan SNP Predesigned Genotyping Assays. The association analysis was performed using SNPStats software and STATISTICA10.

RESULTS

The association between IL12B polymorphism and viruria was observed ( = 0.029). In multiple comparison tests, heterozygous T/G genotype of IL12B was associated with higher viruria than T/T genotype ( = 0.041) in cCMV-infected newborns. In allele analysis, T allele of IL12B was associated with higher viremia ( = 0.037) in symptomatic newborns. We observed higher VL in symptomatic newborns in comparison to asymptomatic (median viremia: 1.7 × 10 copies/mL vs. 2.0 × 10 copies/mL ( = 0.002), median viruria: 1.0 × 10 copies/mL versus 6.9 × 10 copies/mL ( = 0.001), respectively).

CONCLUSIONS

IL12B rs3212227 was associated with VL in cCMV. Symptomatic newborns had significantly higher viremia and viruria. The role of SNPs in pathogenesis of cCMV warrants further investigations.

摘要

背景

先天性巨细胞病毒(cCMV)感染中决定病毒载量(VL)的因素数据有限。单核苷酸多态性(SNP)可能影响个体对感染的宿主反应。本研究旨在探讨细胞因子或细胞因子受体基因编码 SNP 与先天性巨细胞病毒感染新生儿 VL 之间的关系。

材料和方法

采用 TaqMan SNP 预设计基因分型检测,对包括 92 例 cCMV 感染新生儿(73 例有症状,19 例无症状)在内的 233 例新生儿研究人群中的 8 个 SNP(IL1B rs16944、IL12B rs3212227、IL28B rs12979860、CCL2 rs1024611、DC-SIGN rs735240、TLR2 rs5743708、TLR4 rs4986791 和 TLR9 rs352140)进行了分析。采用 SNPStats 软件和 STATISTICA10 进行关联分析。

结果

观察到 IL12B 多态性与尿病毒之间存在关联( = 0.029)。在多重比较检验中,cCMV 感染新生儿中 IL12B 的杂合 T/G 基因型与 T/T 基因型相比,尿病毒更高( = 0.041)。在等位基因分析中,IL12B 的 T 等位基因与有症状新生儿的病毒血症更高相关( = 0.037)。与无症状新生儿相比,我们观察到有症状新生儿的 VL 更高(中位数病毒血症:1.7×10 拷贝/mL 与 2.0×10 拷贝/mL( = 0.002),中位数尿病毒:1.0×10 拷贝/mL 与 6.9×10 拷贝/mL( = 0.001))。

结论

IL12B rs3212227 与 cCMV 的 VL 相关。有症状的新生儿有明显更高的病毒血症和尿病毒。SNP 在 cCMV 发病机制中的作用值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7c6/8330360/1e8f0a301eb3/jmotherandchild-24-009-g001.jpg

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