Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Dzieci Polskich 20, 04-730, Warsaw, Poland.
Department of Neonatology and Neonatal Intensive Care, The Children's Memorial Health Institute, Warsaw, Poland.
Eur J Clin Microbiol Infect Dis. 2017 Oct;36(10):1811-1818. doi: 10.1007/s10096-017-2996-6. Epub 2017 May 13.
Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).
巨细胞病毒（CMV）是先天性感染最常见的病毒病原体，也是感音神经性听力损失（SNHL）的主要非遗传原因。导致发育中的胎儿易感染宫内 CMV 并发展为听力损失的宿主免疫因素尚不清楚。本研究旨在评估细胞因子和细胞因子受体基因内多态性与先天性 CMV 感染风险和听力结果之间的潜在关联。一组 11 个候选单核苷酸多态性（SNP）：TNF rs1799964、TNF rs1800629、TNFRSF1A rs4149570、IL1B rs16944、IL1B rs1143634、IL10 rs1800896、IL10RA rs4252279、IL12B rs3212227、CCL2 rs1024611、CCL2 rs13900、CCR5 rs333 在 470 名婴儿（72 名经证实宫内 CMV 感染和 398 名未感染对照）中进行了基因分型，并与先天性 CMV 感染和结果相关。多变量分析显示，IL1B rs16944 TT 和 TNF rs1799964 TC 基因型与宫内 CMV 感染显著相关（OR 分别为 2.32；95%CI，1.11-4.89；p=0.032 和 OR 分别为 2.17；95%CI，1.25-3.77；p=0.007）。72 例先天性感染新生儿中有 22 例确诊为 SNHL。CCL2 rs13900 的 CT 或 TT 基因型携带者出生时和 6 个月时听力损失的风险增加（OR 分别为 3.59；p=0.028 和 OR 分别为 4.10；p=0.039）。这是第一项报道 IL1B、TNF 和 CCL2 中的 SNP 与先天性 CMV 感染易感性（IL1B 和 TNF）和 SNHL（CCL2）之间存在关联的研究。
