Impact of TLR7 and TLR9 polymorphisms on susceptibility to placental infections and pregnancy complications

Sánchez-Luquez, Karen; Schadock, Ines; Gonçalves, Carla Vitola; Tornatore, Michele; Finger‐Jardim, Fabiana; Avila, Emiliana Claro; Soares, Marcelo A.; Martínez, Ana Maria Barral de; Ellwanger, Joel Henrique; Hora, Vanusa Pousada da

doi:10.1016/j.jri.2021.103342

Cited by 9 publications

(5 citation statements)

References 47 publications

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“…These data agree with previous findings of our group that show an association of microcephaly with low producer alleles in genes from the antiviral response 19 . In line with this hypothesis, the presence of the TT genotype for this SNP in the TLR7 gene was previously associated with susceptibility to Herpes simplex virus -1 infection and an increased risk of placental infections 27 . Furthermore, higher levels of CXCL-8 in cerebrospinal fluid were found in neonates without CZS who were born from mothers infected with ZIKV during pregnancy, when compared to those born with microcephaly by CZS, suggesting an important role of this chemokine in protection against CZS 26 .…”

Section: Discussionsupporting

confidence: 59%

“…The SNP rs179008 (A>T) is an intragenic variation and promotes the exchange of glutamine by leucine, affecting the quantity and functionality of the protein, with the T allele linked to the lowest expression of TLR7 and the lowest expression of IFNλ 28 . This variant has been associated with viral infections, being linked to different prognoses 27 , 28 , 63 , 64 . In the present study, an association between the T allele and more severe microcephaly is demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…Here, using hypothesis-driven candidate genes and their previous report in the ZIKV pathogenesis or their function against viral infections or other infection disease, we tested SNPs in TREM1 [20][21][22] , CXCL10 11,23 , IL4 24,25 , CXCL8 26 , TLR3 19 , TLR7 [27][28][29] , IFNR1 30,31 , CXCR1 32 , IL10 [33][34][35] , CCR2 and CCR5 36 genes to investigate their association to CZS, in a cohort of mothers who had delivered CZS infants, their infants and healthy donors.…”

mentioning

confidence: 99%

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Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Santos

Magalhães

Fonseca

et al. 2023

Sci Rep

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Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case–control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Santos

Magalhães

Fonseca

et al. 2023

Sci Rep

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“…Recent studies showed that SLC6A9 [99], FKBP1B [100], S100A12 [101], SLC6A19 [102], TXN (thioredoxin) [103], TLR9 [104], HP (haptoglobin) [105], ARG1 [106], PINK1 [107], B2M [108], C5AR1 [109], MYADM (myeloid associated differentiation marker) [110], CBS (cystathionine beta-synthase) [111], GPX1 [112], SIAH2 [113], PRDX2 [114], RDH8 [115], CYP11B2 [116], RARRES2 [117], NOX1 [118], IL33 [119], OTC (ornithine transcarbamylase) [120], CYP1A1 [121], NFATC4 [122], TSLP (thymic stromal lymphopoietin) [123], WNT4 [124], MGP (matrix Gla protein) [125], FGFBP1 [126], GHR (growth hormone receptor) [127], ERBB3 [128], GFAP (glial fibrillary acidic protein) [129], CCDC40 [130], CACNB2 [131], CD34 [132], NOTCH3 [133], TERT (telomerase reverse transcriptase) [134], GNB3 [135], TP73 [136], RYR2 [137], ENPEP (glutamyl aminopeptidase) [138], SCN7A [139], WNK4 [140], SFRP5 [141], GDF15 [142], CAV1 [143], KCNA5 [144], FOXC1 [145], ASIC1 [146], VASH2 [147], CXCL8 [148], PAPPA2 [149], KCNMA1 [150], LOX (lysyl oxidase) [151], SPARCL1 [152] and CYP3A5 [153] might have the potential to be used as diagnostic biomarkers of hypertension. Previous studies have reported that RHD (Rh blood group D antigen) [154], S100A12 [155], TXN (thioredoxin) [156], TLR9 [157], S100P [158], TAGLN2 [159], S100A9 [160], CA1 [161], HP (haptoglobin) [162], RPL39 [163], F5 [164], PINK1 [165], B2M [166], S100A11 [167], SLC4A1 [168], CBS (cystathionine beta-sy...…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Bipolar disorder (BD), also known as psychiatric disorder, affects millions of people all over the world. The aim of this investigation was to screen and verify hub genes involved in BD as well as to explore potential molecular mechanisms. The next generation sequencing (NGS) dataset GSE124326 was downloaded from the Gene Expression Omnibus (GEO) database, which contained 480 samples, including 240 BD and 240 normal controls. Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. A protein–protein interaction (PPI) network and module analysis were used to identify hub genes. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed. Receiver operating characteristic curve (ROC) analysis was used to validate hub genes. In this work, 957 DEGs, including 477 up regulated and 480 down regulated, were obtained from NGS data. The GO and pathway enrichment analyses of the DEGs showed that the up regulated genes were enriched in the neutrophil degranulation, immune system, transport, cytoplasm and enzyme regulator activity, and the down regulated genes were enriched in extracellular matrix organization, diseases of metabolism, multicellular organismal process, cell periphery and metal ion binding. Finally, through analyzing the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes UBB, UBE2D1, TUBA1A, RPL11, RPS24, NOTCH3, CAV1, CNBD2, CCNA1 and MYH11 by the Cytoscape software. The current investigation illustrates a characteristic NGS data in BD, which might contribute to the interpretation of the progression of BD and provide novel biomarkers and therapeutic targets for BD.

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“…This is especially important during HPV infection, and Hasan et al have found that the papillomavirus suppresses the function of TLR9 via E7, promoting cervical cancer [201]. In pregnant women, Sánchez-Luquez et al have found that TLR 7 and TLR 9 together decrease the risk of placental viral infections by observing the impact of TLR 7 and TLR 9 single nucleotide polymorphisms (SNPs) within the genes of these molecules [202]. Similarly, TLR 3 is highly expressed at the trophoblast level during the first trimester.…”

Section: The Innate Immune Responsementioning

confidence: 99%

Unraveling Immunological Dynamics: HPV Infection in Women—Insights from Pregnancy

Condrat,

Cretoiu,

Radoi

et al. 2023

Viruses

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During pregnancy, hormonal and immune adaptations are vital for supporting the genetically distinct fetus during elevated infection risks. The global prevalence of HPV necessitates its consideration during pregnancy. Despite a seemingly mild immune response, historical gestational viral infections underscore its significance. Acknowledging the established HPV infection risks during pregnancy, our review explores the unfolding immunological changes in pregnant women with HPV. Our analysis aims to uncover strategies for safely modulating the immune system, mitigating adverse pregnancy consequences, and enhancing maternal and child health. This comprehensive narrative review delves into the existing knowledge and studies on this topic.

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Impact of TLR7 and TLR9 polymorphisms on susceptibility to placental infections and pregnancy complications

Cited by 9 publications

References 47 publications

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Unraveling Immunological Dynamics: HPV Infection in Women—Insights from Pregnancy

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