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 ◽  
...  

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.

2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  

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.


2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  

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.


2020 ◽  
Author(s):  
Doreen Mhandire ◽  
Kudakwashe Mhandire ◽  
Mulalo Magadze ◽  
Ambroise Wonkam ◽  
Andre P Kengne ◽  
...  

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.


Author(s):  
Ruth Valentine ◽  
Olushola Ibiyemi ◽  
Anne Maguire ◽  
Fatemeh Vida Zohoori ◽  
Simon Kometa ◽  
...  

Aim: To determine the association between single nucleotide polymorphisms (SNPs) within the COL1A2 gene and dental fluorosis among 4- and 8-year-old Nigerian children. Methods: A cross-sectional study was undertaken among 125 four and eight-year-old Nigerian children living in naturally fluoridated areas of Ibadan, Nigeria. Drinking and cooking water samples were collected for F analysis. Buccal mucosa swabs were collected from all children and genomic DNA extracted. Presence or absence of the SNP within the COL1A2 gene was identified by PCR and DNA sequencing for 70 of the participants. Results: The median (minimum, maximum) F concentration of drinking and cooking water were 0.05 (<0.1, 3.0) mg/L and 0.01 (<0.1, 4.0) mg/L respectively. The majority of the study participants (52.9%) were heterozygous for the SNP. There was a statistically significant association between F concentration in drinking water and the occurrence of dental fluorosis (p=0.04). F concentration in drinking water was the only statistically significant predictor of dental fluorosis (p=0.03, OR=3.64(CI=1.11-11.94)) after adjusting for F concentration in cooking water and SNPs. The risk of dental fluorosis tended to increase with the presence of SNPs AA and AC (RR > 1) but this association was not statistically significant. Conclusion: The majority of the study participants had the heterozygote SNP AC genotype of COL1A2 gene. F concentration in drinking water was the only statistically significant predictor of dental fluorosis. The risk of dental fluorosis tended to increase with the presence of SNPs AA and AC (RR > 1) but was not statistically significant.


2006 ◽  
Vol 6 (4) ◽  
pp. 992-997 ◽  
Author(s):  
I. CAPPUCCIO ◽  
L. PARISET ◽  
P. AJMONE-MARSAN ◽  
S. DUNNER ◽  
O. CORTES ◽  
...  

2011 ◽  
Vol 19 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Catrin E. Moore ◽  
Branwen J. Hennig ◽  
Kirsten P. Perrett ◽  
J. Claire Hoe ◽  
Sue J. Lee ◽  
...  

ABSTRACTThe rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P= 0.004 [unadjusted]) and CD44 (rs12419062) (P= 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.


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