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Plasma advanced oxidative protein products are associated with anti-oxidative stress pathway genes and malaria in a longitudinal cohort.

Zhang G, Skorokhod OA, Khoo SK, Aguilar R, Wiertsema S, Nhabomba AJ, Marrocco T, McNamara-Smith M, Manaca MN, Barbosa A, Quintó L, Hayden CM, Goldblatt J, Guinovart C, Alonso PL, Dobaño C, Schwarzer E, LeSouëf PN - Malar. J. (2014)

Bottom Line: In a longitudinal birth cohort the effects were investigated of genetic polymorphisms in five oxidative pathway genes on AOPP levels.Mixed linear regression analyses found that the single nucleotide polymorphisms GCLC RS10948751 and HMOX1 RS17885925 were significantly associated with AOPP levels (p = 0.030 and p = 0.027, respectively).Several polymorphisms in GCLC, GSR and HMOX1 genes were associated with oxidative stress status of these children.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Paediatrics and Child Health, University of Western Australia, c/o 100 Roberts Rd, Subiaco, WA 6008 Perth, Australia. guicheng.zhang@uwa.edu.au.

ABSTRACT

Background: Advanced oxidation protein products (AOPP) are newly identified efficient oxidative stress biomarkers. In a longitudinal birth cohort the effects were investigated of genetic polymorphisms in five oxidative pathway genes on AOPP levels.

Methods: This study is part of a three-arm randomized, double-blind, placebo-controlled trial. Three hundred and twelve children were included in the present study with AOPP levels measured at 2.5, 5.5, 10.5, 15 and 24 months of age. Twelve polymorphisms were genotyped in five oxidative stress pathway genes: glutathione reductase (GSR), glutamylcysteine synthetase (GCLC), glutathione S-transferase (GST) P1, haem oxygenase 1 (HMOX1) and superoxide dismutase 2 (SOD2) in 298 children. There were 284 children assessed for anaemia and clinical malaria infection at the age of 24 months.

Results: Two principal components (PCA1 and PCA2) were derived from the AOPP levels measured at the five time points. PCA1 was significantly associated with anaemia (p = 0.0002), and PCA2 with clinical malaria infection (p = 0.047). In the K-Means Cluster Analysis based on levels of AOPP, children were clustered into two groups: Group A (lower AOPP levels) and Group B (higher AOPP levels). The cluster membership was significantly associated with anaemia (p =0.003) as well as with the GSR RS3594 polymorphism (p = 0.037). Mixed linear regression analyses found that the single nucleotide polymorphisms GCLC RS10948751 and HMOX1 RS17885925 were significantly associated with AOPP levels (p = 0.030 and p = 0.027, respectively).

Conclusion: Plasma AOPP levels were predictive for anaemia and oxidative stress markers for clinical malaria infection in two year old children. Several polymorphisms in GCLC, GSR and HMOX1 genes were associated with oxidative stress status of these children.

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Related in: MedlinePlus

Associations of plasma AOPP levels (geometric mean and 95% confidence intervals) with the genotypes of GCLC RS10948751 and HMOX1 RS17885925; Mixed linear model was employed and adjusted geometric means (adjusted for age and anaemia) were presented.
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Figure 6: Associations of plasma AOPP levels (geometric mean and 95% confidence intervals) with the genotypes of GCLC RS10948751 and HMOX1 RS17885925; Mixed linear model was employed and adjusted geometric means (adjusted for age and anaemia) were presented.

Mentions: Using a mixed linear regression model, the associations of genotypes were investigated with the AOPP plasma levels measured at the five time points. The model showed that the variables age (the five time points) and anaemia (presence/absence) were significantly associated with the plasma AOPP levels, with the presence of anaemia being associated with higher AOPP levels and age associated with decreased AOPP. After adjusting for age and presence/absence of anaemia the SNPs GCLC RS10948751 and HMOX1 RS17885925 were also significantly associated with the levels of AOPP (p = 0.030 and p = 0.027, respectively). Figure 6 shows the levels of AOPP (adjusted for age and anaemia) for the different genotypes of these two SNPs. In the regression model analysis, the effects of gender, maternal malaria infection and intervention were not significantly associated to the AOPP levels.


Plasma advanced oxidative protein products are associated with anti-oxidative stress pathway genes and malaria in a longitudinal cohort.

Zhang G, Skorokhod OA, Khoo SK, Aguilar R, Wiertsema S, Nhabomba AJ, Marrocco T, McNamara-Smith M, Manaca MN, Barbosa A, Quintó L, Hayden CM, Goldblatt J, Guinovart C, Alonso PL, Dobaño C, Schwarzer E, LeSouëf PN - Malar. J. (2014)

Associations of plasma AOPP levels (geometric mean and 95% confidence intervals) with the genotypes of GCLC RS10948751 and HMOX1 RS17885925; Mixed linear model was employed and adjusted geometric means (adjusted for age and anaemia) were presented.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230024&req=5

Figure 6: Associations of plasma AOPP levels (geometric mean and 95% confidence intervals) with the genotypes of GCLC RS10948751 and HMOX1 RS17885925; Mixed linear model was employed and adjusted geometric means (adjusted for age and anaemia) were presented.
Mentions: Using a mixed linear regression model, the associations of genotypes were investigated with the AOPP plasma levels measured at the five time points. The model showed that the variables age (the five time points) and anaemia (presence/absence) were significantly associated with the plasma AOPP levels, with the presence of anaemia being associated with higher AOPP levels and age associated with decreased AOPP. After adjusting for age and presence/absence of anaemia the SNPs GCLC RS10948751 and HMOX1 RS17885925 were also significantly associated with the levels of AOPP (p = 0.030 and p = 0.027, respectively). Figure 6 shows the levels of AOPP (adjusted for age and anaemia) for the different genotypes of these two SNPs. In the regression model analysis, the effects of gender, maternal malaria infection and intervention were not significantly associated to the AOPP levels.

Bottom Line: In a longitudinal birth cohort the effects were investigated of genetic polymorphisms in five oxidative pathway genes on AOPP levels.Mixed linear regression analyses found that the single nucleotide polymorphisms GCLC RS10948751 and HMOX1 RS17885925 were significantly associated with AOPP levels (p = 0.030 and p = 0.027, respectively).Several polymorphisms in GCLC, GSR and HMOX1 genes were associated with oxidative stress status of these children.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Paediatrics and Child Health, University of Western Australia, c/o 100 Roberts Rd, Subiaco, WA 6008 Perth, Australia. guicheng.zhang@uwa.edu.au.

ABSTRACT

Background: Advanced oxidation protein products (AOPP) are newly identified efficient oxidative stress biomarkers. In a longitudinal birth cohort the effects were investigated of genetic polymorphisms in five oxidative pathway genes on AOPP levels.

Methods: This study is part of a three-arm randomized, double-blind, placebo-controlled trial. Three hundred and twelve children were included in the present study with AOPP levels measured at 2.5, 5.5, 10.5, 15 and 24 months of age. Twelve polymorphisms were genotyped in five oxidative stress pathway genes: glutathione reductase (GSR), glutamylcysteine synthetase (GCLC), glutathione S-transferase (GST) P1, haem oxygenase 1 (HMOX1) and superoxide dismutase 2 (SOD2) in 298 children. There were 284 children assessed for anaemia and clinical malaria infection at the age of 24 months.

Results: Two principal components (PCA1 and PCA2) were derived from the AOPP levels measured at the five time points. PCA1 was significantly associated with anaemia (p = 0.0002), and PCA2 with clinical malaria infection (p = 0.047). In the K-Means Cluster Analysis based on levels of AOPP, children were clustered into two groups: Group A (lower AOPP levels) and Group B (higher AOPP levels). The cluster membership was significantly associated with anaemia (p =0.003) as well as with the GSR RS3594 polymorphism (p = 0.037). Mixed linear regression analyses found that the single nucleotide polymorphisms GCLC RS10948751 and HMOX1 RS17885925 were significantly associated with AOPP levels (p = 0.030 and p = 0.027, respectively).

Conclusion: Plasma AOPP levels were predictive for anaemia and oxidative stress markers for clinical malaria infection in two year old children. Several polymorphisms in GCLC, GSR and HMOX1 genes were associated with oxidative stress status of these children.

Show MeSH
Related in: MedlinePlus