Mhandire Doreen Z, Mhandire Kudakwashe, Magadze Mulalo, Wonkam Ambroise, Kengne Andre P, Dandara Collet
Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
BMC Med Genet. 2020 May 25;21(1):113. doi: 10.1186/s12881-020-01044-8.
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.
孕期母体巨细胞病毒（CMV）感染和/或再激活与众多不良婴儿结局相关。然而，宿主基因多态性在调节母体CMV状态中的作用尚无定论。本研究调查了津巴布韦黑人中Toll样受体（TLR）和细胞因子基因单核苷酸多态性与母体血浆CMV DNA状态之间可能存在的关联。
在一项横断面研究中，纳入了110名孕晚期妇女，其中包括36例CMV感染病例以及74例年龄和HIV状态相匹配的未感染CMV的对照。使用Agena MassARRAY®系统上的iplex GOLD SNP基因分型方案对10个编码参与抗CMV免疫蛋白的基因中的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）多态性与CMV阳性（CMV+）状态相关，而TLR9 rs352139T>C（p=0.049）多态性与CMV+状态的关联处于临界值。相反，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，TLR2、TLR4、TLR9、TLR7、IL-6、IL-10、IL-28B、IL-1A和干扰素AR1（IFNAR1）基因单核苷酸多态性的等位基因频率在津巴布韦人群中首次被报道。津巴布韦人群中的等位基因频率总体上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基因多态性影响津巴布韦黑人孕晚期的CMV状态。这可能归因于在先前暴露于CMV感染的人群中对CMV再激活的免疫反应可能受到调节。
