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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

AOPP levels at the five time points and PCA scores stratified by cluster membership. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores; Cluster membership was clarified using K-Means Cluster Analysis.
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Figure 1: AOPP levels at the five time points and PCA scores stratified by cluster membership. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores; Cluster membership was clarified using K-Means Cluster Analysis.

Mentions: Based on the levels of AOPP at the five time points, the children were clustered into two groups: Group A (lower AOPP levels) and Group B (higher AOPP levels). Group A included 161 children and Group B included 151 children. It was expected that the cluster membership would be associated with the levels of AOPP at the five time points as well as to the two PCA components, as the membership was defined from the levels of AOPP. Figure 1 shows the differences in the levels of AOPP (Figure 1A) and in the two principal components (Figure 1B) between children in Group A and Group B. Children in Group A had consistently and significantly lower levels of AOPP at the five time points, and lower scores of PCA1 (p < 0.0001).


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)

AOPP levels at the five time points and PCA scores stratified by cluster membership. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores; Cluster membership was clarified using K-Means Cluster Analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: AOPP levels at the five time points and PCA scores stratified by cluster membership. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores; Cluster membership was clarified using K-Means Cluster Analysis.
Mentions: Based on the levels of AOPP at the five time points, the children were clustered into two groups: Group A (lower AOPP levels) and Group B (higher AOPP levels). Group A included 161 children and Group B included 151 children. It was expected that the cluster membership would be associated with the levels of AOPP at the five time points as well as to the two PCA components, as the membership was defined from the levels of AOPP. Figure 1 shows the differences in the levels of AOPP (Figure 1A) and in the two principal components (Figure 1B) between children in Group A and Group B. Children in Group A had consistently and significantly lower levels of AOPP at the five time points, and lower scores of PCA1 (p < 0.0001).

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