scholarly journals Genetic variation in toll like Receptor 2, 7, 9 and interleukin-6 influences risk of Cytomegalovirus infection in pregnancy

2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Maternal Plasma ◽  
Late Gestation ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Cmv Infection ◽  
Infant Outcomes ◽  
Host Genetic ◽  
Cmv Status ◽  
In Pregnancy

Abstract 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. Results: The TLR2 rs1816702C/C (p=0.002), TLR7 rs179008C/C (p<0.001) and TLR9 rs352139C/C (p=0.003) genotypes were associated with a CMV+ status. In contrast, the interleukin ( IL)-6 rs10499563T/C TLR2 rs1816702C/C (p=0.002) genotype was associated (p<0.001) with CMV- status. Furthermore, genotype and 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 in a Zimbabwean population. 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 that was previously exposed to CMV infection.

scholarly journals Genetic variation in toll like Receptors 2, 7, 9 and interleukin-6 is associated with Cytomegalovirus infection in late pregnancy

2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genetic Polymorphisms ◽  
Allele Frequencies ◽  
Late Gestation ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Cmv Infection ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Cmv Status

Abstract 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 re 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.

scholarly journals Genetic variation in toll like Receptors 2, 7, 9 and interleukin-6 is associated with Cytomegalovirus infection in late pregnancy

2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genetic Polymorphisms ◽  
Allele Frequencies ◽  
Late Gestation ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Cmv Infection ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Cmv Status

Abstract 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 re 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.

scholarly journals Genetic variation in toll like Receptors 2, 7, 9 and interleukin-6 is associated with Cytomegalovirus infection in late pregnancy 

2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Genetic Polymorphisms ◽  
Allele Frequencies ◽  
Late Gestation ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Cmv Infection ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Cmv Status

Abstract 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 (SNPs) 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 and (p<0.001) 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 re 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.

scholarly journals Lesion size is associated with genetic polymorphisms in TLR1, TLR6, and TIRAP genes in patients with major abscesses and diabetic foot infections

2019 ◽  
Vol 39 (2) ◽  
pp. 353-360 ◽  
Author(s):  
Valentino D’Onofrio ◽  
Annelie A. Monnier ◽  
Cécile Kremer ◽  
Mark H. T. Stappers ◽  
Mihai G. Netea ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Diabetic Foot ◽  
Lesion Size ◽  
Allelic Variant ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Linear Regression Models ◽  
Single Nucleotide ◽  
Diabetic Foot Infections ◽  
Complicated Skin

AbstractGenetic variation in Toll-like receptors (TLRs) has previously been associated with susceptibility to complicated skin and skin structure infections (cSSSIs). The aim of this study was to investigate associations between the severity of cSSSIs, i.e., major abscesses and diabetic foot infections (DFIs), and a set of genetic polymorphisms in the Toll-like receptor pathway. A total of 121 patients with major abscesses and 132 with DFIs participating in a randomized clinical trial were genotyped for 13 nonsynonymous single-nucleotide polymorphisms (SNPs) in genes coding for TLRs and the signaling adaptor molecule TIRAP. Infection severity was defined by lesion size at clinical presentation for both types of infections. The PEDIS infection score was also used to define severity of DFIs. Linear regression models were used to study factors independently associated with severity. In patients with large abscesses, hetero- or homozygosity for the allelic variant TLR6 (P249S) was associated with significantly smaller lesions while homozygosity for the allelic variant TLR1 (R80T) was associated with significantly larger lesions. PRRs genes were not significantly associated with PEDIS. However, patients with DFI hetero- or homozygous for the allelic variant TLR1 (S248N) had significantly larger lesions. Polymorphisms in TLR1 and TLR6 influence the severity of cSSSIs as assessed by the lesion size of major abscesses and DFIs. ClinicalTrial.gov Identifier: NCT 00402727

Caloric restriction, but not caloric loading, affects circulating fetal and maternal C-type natriuretic peptide concentrations in late ovine gestation

2012 ◽  
Vol 24 (8) ◽  
pp. 1063 ◽  
Author(s):  
B. A. McNeill ◽  
G. K. Barrell ◽  
M. J. Ridgway ◽  
M. P. Wellby ◽  
T. C. R. Prickett ◽  
...  
Keyword(s):  
Growth Factor ◽  
Caloric Restriction ◽  
Natriuretic Peptide ◽  
Nutrient Status ◽  
Maternal Plasma ◽  
Nutrient Supply ◽  
Late Gestation ◽  
Short Term ◽  
Fetal Plasma ◽  
In Pregnancy

The factors regulating the greatly elevated concentrations of maternal plasma C-type natriuretic peptide (CNP) forms in ruminant pregnancy are largely unknown, but nutrient status is likely to be important. Previous work has shown that increases in maternal plasma CNP, sourced from the placenta, occur in response to caloric restriction in late gestation. Whether oversupply of nutrients also regulates CNP secretion in pregnancy has not been studied. Hypothesising that CNP in fetal and maternal tissues will be responsive to both deficiency and excess, we studied changes in CNP and a cosecreted fragment, namely N-terminal pro-CNP (NTproCNP), during short-term periods of caloric restriction (CR) and loading (CL). Twin-bearing ewes received CR (fasted Days 121–124), CL (Days 110–124) or control maintenance diets. During CR, fetal plasma CNP forms, insulin-like growth factor (IGF)-1 and liveweight all fell, and maternal plasma NTproCNP increased. During CL, fetal IGF-1 increased, whereas CNP forms and liveweight were unchanged, as were maternal concentrations of CNP forms. The high abundance of CNP peptides in placental tissues was unaffected by these short-term changes in nutrient supply. We conclude that CNP in the fetal–maternal unit is acutely responsive to undernutrition, but is unaffected by oversupply in late gestation.

scholarly journals Molecular Investigation of Association Among Common IL-6 Polymorphism with Cytomegalovirus(CMV) Infection and Recurrent Miscarriage in Iranian Women

2021 ◽  
Author(s):  
Parisa Pourroostaei Ardakani ◽  
Bahareh Rahimi ◽  
Mohammad Panahi ◽  
Babak Karimian ◽  
Hamzeh Rahimi
Keyword(s):  
Recurrent Miscarriage ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Iranian Women ◽  
Cmv Infection ◽  
Single Nucleotide ◽  
Host Genetic ◽  
Control Study ◽  
Healthy Females

Abstract Background: Recurrent pregnancy loss (RPL) is described as two or more spontaneous abortions. Until now, although various factors such as genetic, endocrinology, anatomy, immunology, and microbiology have been distinguished that affect abortions, the precise basic etiology in up to 50% of RPL cases are not determined. Human cytomegalovirus (CMV) infection and host genetic background, like IL-6 SNP polymorphisms play important roles in RPL etiology. Objective: This study aimed to evaluate relationship among single nucleotide polymorphisms (-634C/G and -174 G/C) in the IL-6 gene with CMV infection and risk of RPL for early detection and treatment of RPL. Materials and methods: This case-control study was carried on 80 Iranian females with RPL and 80 healthy females as control group. The extraction of DNA from samples and detection of CMV and IL6 SNPs were determined by Tetra ARMS-PCR. Finally, the statistical analysis for detection CMV and two polymorphisms roles in RPL were analyzed by Epi Info TM software by X2 test. Results: Our results indicated an increased rate of CMV infection in RPL group (44%) versus the control group (25.45%). Also, the prevalence of IL-6 -634C/G genotype among RPL patients with CMV infection was 80%, while the frequency of this genotype among RPL patients without CMV infection was 50%. Furthermore, no substantial relation was found between IL-6 -174 G/C genotypes and RPL (P ≤0.0001). BesidesConclusion: This study not only indicated a significant role of CMV in RPL, but also showed CMV association with allele G in IL6 -634 among Iranian women. In addition, suggested the use of CMV and IL-6 -634 GG genotypes in RPL as diagnostic and prognostic biomarkers in Iranian population.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea

2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske
Keyword(s):  
Late Onset ◽  
Adult Population ◽  
Additive Models ◽  
Atopic Asthma ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Single Nucleotide ◽  
Gender And Age

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

Pharmacokinetics, Placental and Breast Milk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV

2019 ◽  
Vol 25 (5) ◽  
pp. 556-576 ◽  
Author(s):  
E.M. Hodel ◽  
C. Marzolini ◽  
C. Waitt ◽  
N. Rakhmanina
Keyword(s):  
Breast Milk ◽  
Protease Inhibitors ◽  
Drug Class ◽  
Drug Transporters ◽  
Maternal Plasma ◽  
Antiretroviral Drugs ◽  
Physiological Changes ◽  
Women Living With Hiv ◽  
Living With Hiv ◽  
In Pregnancy

Background:Remarkable progress has been achieved in the identification of HIV infection in pregnant women and in the prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breast milk. We also summarized main safety considerations for in utero and breast milk ARVs exposures in infants.Methods:We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breast milk transport of ARVs, we selected the studies that provided ratios of maternal to the cord (M:C) plasma and breast milk to maternal plasma (M:P) concentrations, respectively.Results:We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect the dosing of several protease inhibitors during pregnancy and limit the use of several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed the currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breast milk and summarized the effect of pregnancy on placental and of breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs.Conclusions:Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal, and consequently, fetal ARV exposure. Limited available data suggest that the expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breast milk. The drug transporter’s role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.

Host genetic polymorphisms associated with beta human papillomavirus seropositivity

2021 ◽  
Author(s):  
Annika Antonsson ◽  
Astrid J. Rodriguez-Acevedo ◽  
Upekha E. Liyanage ◽  
Maria Celia B. Hughes ◽  
Jolieke C. van der Pols ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Genetic Polymorphisms ◽  
Host Genetic

scholarly journals LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Polymorphisms ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Obstructive Pulmonary Disease ◽  
Logistic Analysis ◽  
Copd Patients ◽  
Increased Risk ◽  
And Gender

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

Sign in / Sign up

Export Citation Format

Share Document