Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy

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dc.contributor.authorMhandire, Doreen Z
dc.contributor.authorMhandire, Kudakwashe
dc.contributor.authorMagadze, Mulalo
dc.contributor.authorWonkam, Ambroise
dc.contributor.authorKengne, Andre P
dc.contributor.authorDandara, Collet
dc.date.accessioned2020-06-11T17:20:30Z
dc.date.available2020-06-11T17:20:30Z
dc.date.issued2020-05-25
dc.date.updated2020-05-31T03:15:33Z
dc.description.abstractBackground 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. Methods 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. Results 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. Conclusions 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.en_US
dc.identifier.apacitationMhandire, D. Z., Mhandire, K., Magadze, M., Wonkam, A., Kengne, A. P., & Dandara, C. (2020). Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy. <i>BMC Medical Genetics</i>, 21(1), 113. http://hdl.handle.net/11427/32069en_ZA
dc.identifier.chicagocitationMhandire, Doreen Z, Kudakwashe Mhandire, Mulalo Magadze, Ambroise Wonkam, Andre P Kengne, and Collet Dandara "Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy." <i>BMC Medical Genetics</i> 21, 1. (2020): 113. http://hdl.handle.net/11427/32069en_ZA
dc.identifier.citationMhandire, D.Z., Mhandire, K., Magadze, M., Wonkam, A., Kengne, A.P. & Dandara, C. 2020. Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy. <i>BMC Medical Genetics.</i> 21(1):113. http://hdl.handle.net/11427/32069en_ZA
dc.identifier.ris TY - Journal Article AU - Mhandire, Doreen Z AU - Mhandire, Kudakwashe AU - Magadze, Mulalo AU - Wonkam, Ambroise AU - Kengne, Andre P AU - Dandara, Collet AB - Background 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. Methods 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. Results 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. Conclusions 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. DA - 2020-05-25 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Medical Genetics KW - Cytomegalovirus KW - Toll-like receptors KW - Interleukins KW - CMV DNA KW - Zimbabwe LK - https://open.uct.ac.za PY - 2020 T1 - Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy TI - Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy UR - http://hdl.handle.net/11427/32069 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12881-020-01044-8
dc.identifier.urihttp://hdl.handle.net/11427/32069
dc.identifier.vancouvercitationMhandire DZ, Mhandire K, Magadze M, Wonkam A, Kengne AP, Dandara C. Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy. BMC Medical Genetics. 2020;21(1):113. http://hdl.handle.net/11427/32069.en_ZA
dc.language.isoenen_US
dc.language.rfc3066en
dc.publisher.departmentDepartment of Pathologyen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceBMC Medical Geneticsen_US
dc.source.journalissue1en_US
dc.source.journalvolume21en_US
dc.source.pagination113en_US
dc.source.urihttps://bmcmedgenet.biomedcentral.com/
dc.subjectCytomegalovirusen_US
dc.subjectToll-like receptorsen_US
dc.subjectInterleukinsen_US
dc.subjectCMV DNAen_US
dc.subjectZimbabween_US
dc.titleGenetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancyen_US
dc.typeJournal Articleen_US
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