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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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AOPP levels at the five time points and PCA scores (mean and 95% confidence intervals) stratified by anaemia at two years. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores (geometric mean and 95% confidence intervals); Anaemia was defined at age two years.
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Figure 2: AOPP levels at the five time points and PCA scores (mean and 95% confidence intervals) stratified by anaemia at two years. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores (geometric mean and 95% confidence intervals); Anaemia was defined at age two years.

Mentions: Among the 284 children who were followed up to the age of 24 months, 23 (8.1%) had anaemia and 32 (11.3%) had clinical malaria infection at this last time point. Generally, children with anaemia at 24 months had higher levels of plasma AOPP at all five time points, with significant differences at ages 2.5 months (p = 0.014) and 15 months (p = 0.001) (Figure 2A). Children with anaemia at 24 months had significantly higher PCA1 scores (p = 0.0002), but not higher PCA2 (Figure 2B). Children with clinical malaria infection at age 24 months did not have significantly higher AOPP levels at ages 2.5, 5.5, 10.5 and 15 months, but had significantly higher AOPP levels at 24 months (Figure 3A). Clinical malaria infection at age 24 months did not associate with PCA1, but was significantly associated with an increased PCA2 (p = 0.047) (Figure 3B).


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 (mean and 95% confidence intervals) stratified by anaemia at two years. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores (geometric mean and 95% confidence intervals); Anaemia was defined at age two years.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: AOPP levels at the five time points and PCA scores (mean and 95% confidence intervals) stratified by anaemia at two years. A: AOPP levels (geometric mean and 95% confidence intervals) at the five time points; B: PCA scores (geometric mean and 95% confidence intervals); Anaemia was defined at age two years.
Mentions: Among the 284 children who were followed up to the age of 24 months, 23 (8.1%) had anaemia and 32 (11.3%) had clinical malaria infection at this last time point. Generally, children with anaemia at 24 months had higher levels of plasma AOPP at all five time points, with significant differences at ages 2.5 months (p = 0.014) and 15 months (p = 0.001) (Figure 2A). Children with anaemia at 24 months had significantly higher PCA1 scores (p = 0.0002), but not higher PCA2 (Figure 2B). Children with clinical malaria infection at age 24 months did not have significantly higher AOPP levels at ages 2.5, 5.5, 10.5 and 15 months, but had significantly higher AOPP levels at 24 months (Figure 3A). Clinical malaria infection at age 24 months did not associate with PCA1, but was significantly associated with an increased PCA2 (p = 0.047) (Figure 3B).

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