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Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy.
BMC Medical Genetics Pub Date : 2020-05-25 , DOI: 10.1186/s12881-020-01044-8
Doreen Z Mhandire 1, 2 , Kudakwashe Mhandire 1, 2 , Mulalo Magadze 1, 2 , Ambroise Wonkam 1, 2 , Andre P Kengne 3, 4 , Collet Dandara 1, 2
Affiliation  

Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R. The TLR7 rs179008A > T (p < 0.001) polymorphism was associated while the TLR9 rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6 rs10499563T > C (p < 0.001) and TLR2 rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7, IL-6, IL-10, IL-28B, IL-1A and interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations. Toll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.

中文翻译:

Toll 样受体 2、7、9 和白细胞介素 6 的遗传变异与妊娠晚期巨细胞病毒感染有关。

孕期母体巨细胞病毒 (CMV) 感染和/或再激活与多种不良婴儿结局相关。然而,宿主遗传多态性在调节母体 CMV 状态中的作用尚无定论。本研究调查了津巴布韦黑人 Toll 样受体 (TLR) 和细胞因子基因中的单核苷酸多态性与母体血浆 CMV DNA 状态之间的可能关联。在一项横断面研究中,纳入了 110 名妊娠晚期妇女,其中包括 36 名 CMV 感染病例和 74 名 CMV 未感染病例,年龄和 HIV 状况匹配的对照。使用 Iplex GOLD SNP 基因分型方案在 Agena MassARRAY® 系统上对编码参与 CMV 免疫的蛋白质的 10 个基因中的 20 个单核苷酸多态性进行基因分型。使用 Stata SE 以及统计软件包 R 的“Genetics”和“SNPassoc”软件包进行统计分析。TLR7 rs179008A > T (p < 0.001) 多态性相关,而 TLR9 rs352139T > C (p = 0.049) 多态性处于开启状态。与 CMV 阳性 (CMV+) 状态相关的边界。相比之下,白细胞介素 (IL)-6 rs10499563T > C (p < 0.001) 和 TLR2 rs1816702C > T (p = 0.001) 多态性与 CMV 阴性 (CMV-) 状态相关。此外,首次在津巴布韦人群中报告了 TLR2、TLR4、TLR9、TLR7、IL-6、IL-10、IL-28B、IL-1A 和干扰素 AR1 (IFNAR1) 基因中 SNP 的等位基因频率。津巴布韦人群的等位基因频率通常与其他非洲人群相当,但与欧洲和亚洲人群相比有所不同。Toll 样受体和白细胞介素遗传多态性影响津巴布韦黑人妊娠晚期 CMV 状态。这归因于先前暴露于 CMV 感染的人群中对 CMV 重新激活的免疫反应可能受到调节。
更新日期:2020-05-25
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