Laboratory of Molecular Biology, School of Medicine, Universidade Federal do Rio Grande (FURG), Rio Grande, Rio Grande do Sul, Brazil.
Laboratory of Molecular Biology, School of Medicine, Universidade Federal do Rio Grande (FURG), Rio Grande, Rio Grande do Sul, Brazil.
J Reprod Immunol. 2021 Aug;146:103342. doi: 10.1016/j.jri.2021.103342. Epub 2021 Jun 2.
This study evaluated the impact of the TLR7 Gln11Leu (rs179008) and TLR9 -1237 T/C (rs5743836) single nucleotide polymorphisms (SNPs) on susceptibility to placental infections and pregnancy complications in 455 Brazilian women. Demographic, socioeconomic, gynecological, and clinical characteristics of the women were collected. Placental tissues were sampled from pregnant women and human and viral DNA was extracted. Human alphaherpesvirus 1 (Herpes simplex virus type 1, HSV-1), Human alphaherpesvirus 2 (Herpes simplex virus type 2, HSV-2) and Human betaherpesvirus 5 (Human cytomegalovirus, HCMV) were detected by nested PCR. TLR9 and TLR7 SNPs were genotyped by PCR amplification of bi-directional specific alleles (Bi-PASA) and restriction fragment length polymorphism (RFLP), respectively. Infections at the time of birth were detected in 45.71 % of women. The presence of the TT genotype (recessive model) of the TLR7 SNP was associated with increased susceptibility to HSV-1 infection (O.R. = 2.23, p = 0.05). The presence of the C allele of the TLR9 SNP, in heterozygosis or homozygosis (dominant model), decreased the infection risk by HCMV (O.R. = 0.31, p-mod<0.05). The TT genotype (recessive model) of the TLR7 SNP was significantly associated (p < 0.05) with increased occurrence of pre-treated hypertension. The codominant model of the TLR9 SNP was significantly associated (p < 0.05) with reduced risk of hospitalization during pregnancy. In combination, the AA/CT (TLR7-TLR9) genotypes significantly decreased the risk of placental infection by HSV-1 and/or HSV-2 (O.R. = 0.47, p = 0.02), the susceptibility to all infectious agents considered in combination (O.R. = 0.4, p = 0.00), and the need of hospitalization (O.R. = 0.48, p = 0.02). In conclusion, TLR7 and TLR9 SNPs are potential modulating factors for the risk of placental infections and pregnancy complications.
本研究评估了 TLR7 Gln11Leu（rs179008）和 TLR9-1237 T/C（rs5743836）单核苷酸多态性（SNP）对 455 名巴西女性胎盘感染和妊娠并发症易感性的影响。收集了女性的人口统计学、社会经济、妇科和临床特征。从孕妇中采集胎盘组织，提取人及病毒 DNA。采用巢式 PCR 检测人α疱疹病毒 1（单纯疱疹病毒 1 型，HSV-1）、人α疱疹病毒 2（单纯疱疹病毒 2 型，HSV-2）和人β疱疹病毒 5（人巨细胞病毒，HCMV）。TLR9 和 TLR7 SNP 通过双向特异性等位基因 PCR 扩增（Bi-PASA）和限制性片段长度多态性（RFLP）分别进行基因分型。在出生时检测到 45.71%的女性存在感染。TLR7 SNP 的 TT 基因型（隐性模型）与 HSV-1 感染易感性增加相关（OR=2.23，p=0.05）。TLR9 SNP 的 C 等位基因（杂合或纯合，显性模型）降低了 HCMV 感染风险（OR=0.31，p<0.05）。TLR7 SNP 的 TT 基因型（隐性模型）与预处理高血压的发生显著相关（p<0.05）。TLR9 SNP 的共显性模型与怀孕期间住院风险降低显著相关（p<0.05）。此外，TLR7-TLR9 的 AA/CT 基因型显著降低了 HSV-1 和/或 HSV-2 引起的胎盘感染风险（OR=0.47，p=0.02）、联合考虑所有感染因子的易感性（OR=0.4，p=0.00）和住院需求（OR=0.48，p=0.02）。总之，TLR7 和 TLR9 SNP 是胎盘感染和妊娠并发症风险的潜在调节因素。
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