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

scholarly journals Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eric H. Decloedt ◽  
Phumla Z. Sinxadi ◽  
Lubbe Wiesner ◽  
John A. Joska ◽  
David W. Haas ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
South African ◽  
Genetic Polymorphisms ◽  
Geometric Mean ◽  
Hiv Positive ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Linear Regression Models ◽  
Single Nucleotide ◽  
Black South African

Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration.Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine.Method: We collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold.Results: The geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing.Conclusion: No genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine.

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.

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.

Genetic Polymorphisms and the Risk of Diabetic Foot: A Systematic Review and Meta-Analyses

2020 ◽  
pp. 153473462097759
Author(s):  
Jun Zhao ◽  
Le-Xuan Zhang ◽  
Yu-Ting Wang ◽  
Yang Li ◽  
Hong-Lin Chen, MD
Keyword(s):  
Genetic Polymorphisms ◽  
Diabetic Foot ◽  
Protective Factor ◽  
Meta Analysis ◽  
Nucleotide Polymorphisms ◽  
Asian Populations ◽  
Tnf Α ◽  
Newcastle Ottawa Scale ◽  
Meta Analyses ◽  
Relationship Of

Background Diabetic foot (DF) is a dangerous complication of diabetes. The aim of the study was to synthesize all the published single nucleotide polymorphisms (SNPs) of DF to objectively evaluate the relationship of SNPs and DF risks. Methods The HuGE database and CNKI were searched for eligible publications on genetic polymorphisms and the risk of DF systematically. The quality of literatures was evaluated by the Newcastle-Ottawa scale. Pooled odds ratios with a 95% confidence interval for SNPs were evaluated through 3 genetic models. Results Citing 29 different polymorphisms from 24 articles and the study met our selection criteria. There were 24 polymorphisms summarized systematically, and 5 merged polymorphisms for a meta-analysis: 9 positively associated with DF: HIF-1α rs11549465, TNF-α rs1800629, TLR-9 rs5743836, FIB rs6056, HSP70-2437C/T, VDR rs2228570, LOX rs1800449, ITLN1 rs2274907, and OPG rs2073617, but OPG rs3134069 was not a risk factor in DF; 6 negatively associated with DF: VEGF rs833061 and rs2010963, MCP-1 rs1024611, SDF-1 rs1801157, SIRT1 rs12778366, and OPG rs2073617. In addition, 13 polymorphisms were not associated with DF: MMP-9 rs3918242, eNOS rs1799983, VEGF rs3025039, -7C/T, rs1570360, rs13207351, and rs699947, IL-6 rs1800795, HIF-1α rs11549467, TNF-α rs361525, TLR-2 rs3804100, SIRT1 rs3758391, and TIMP-1 rs2070584. Conclusions The study provided some evidence for SNPs to the development of diabetic foot. The meta-analysis showed that rs1024611 of MCP-1 may be regarded as a protective factor, especially in Asian populations. Other loci indicated inconsistent results.

scholarly journals Insight into Gene Polymorphisms Involved in Toll-Like Receptor/Interferon Signalling Pathways for Systemic Lupus Erythematosus in South East Asia

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Hwa Chia Chai ◽  
Kek Heng Chua ◽  
Soo Kun Lim ◽  
Maude Elvira Phipps
Keyword(s):  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Signalling Pathways ◽  
Type I ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Interferon Signalling

Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms withinTNFAIP3,STAT4,andIRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles ofSTAT4rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P=0.028, odds ratio(OR)=1.42;P=0.035,OR=1.80, respectively). Polymorphisms inTNFAIP3andIRF5did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated thatSTAT4rs10168266 was significantly associated with the Malaysian SLE as a whole (P=0.014;OR=1.435). The meta-analysis ofSTAT4rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 andPvalue of <0.001.

scholarly journals Toll-Like Receptor 4 Polymorphism Associated with the Response to Whole-Cell Pertussis Vaccination in Children from the KOALA Study

2007 ◽  
Vol 14 (10) ◽  
pp. 1377-1380 ◽  
Author(s):  
Sander Banus ◽  
Renske W. B. Bottema ◽  
Christine L. E. Siezen ◽  
Rob J. Vandebriel ◽  
Johan Reimerink ◽  
...  
Keyword(s):  
Antibody Response ◽  
Pertussis Toxin ◽  
Immunoglobulin G ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Single Nucleotide ◽  
Whole Cell ◽  
Specific Immunoglobulin ◽  
Lower Titer

ABSTRACT We examined the association between haplotype tagging single-nucleotide polymorphisms in TLR4 and the pertussis toxin-specific immunoglobulin G response after whole-cell pertussis (wP) vaccination in 515 1-year-old children from the KOALA study. A lower titer was associated with the minor allele of rs2770150, supporting a role for Toll-like receptor 4 in the antibody response to wP vaccination.

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