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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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Associations of the GSR RS3594 genotype with the cluster membership and with anaemia; Chi-square tests were used. A: GSR RS3594 and cluster membership; B. GSR RS3594 and anaemia.
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Figure 5: Associations of the GSR RS3594 genotype with the cluster membership and with anaemia; Chi-square tests were used. A: GSR RS3594 and cluster membership; B. GSR RS3594 and anaemia.

Mentions: The associations of the different genotypes were investigated in the five oxidative pathway genes with the two PCA scores, with the cluster membership and with anaemia. No significant association was found with PCA1, however GCLC RS10948751 was significantly associated with PCA2 (Figure 4). No genotypes were associated with the cluster membership except for RS3594 in GSR (Figure 5A). The CC homozygotes had a significantly higher percentage of Group B compared with children with CA or AA genotypes (52.6% vs. 36.5%, p = 0.037) (Figure 5A). The CC homozygotes also had a higher percentage of anaemia relative to children with CA or AA genotypes, but this difference was not statistically significant (9.3% vs. 2.2%, p = 0.11) (Figure 5B).


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 the GSR RS3594 genotype with the cluster membership and with anaemia; Chi-square tests were used. A: GSR RS3594 and cluster membership; B. GSR RS3594 and anaemia.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Associations of the GSR RS3594 genotype with the cluster membership and with anaemia; Chi-square tests were used. A: GSR RS3594 and cluster membership; B. GSR RS3594 and anaemia.
Mentions: The associations of the different genotypes were investigated in the five oxidative pathway genes with the two PCA scores, with the cluster membership and with anaemia. No significant association was found with PCA1, however GCLC RS10948751 was significantly associated with PCA2 (Figure 4). No genotypes were associated with the cluster membership except for RS3594 in GSR (Figure 5A). The CC homozygotes had a significantly higher percentage of Group B compared with children with CA or AA genotypes (52.6% vs. 36.5%, p = 0.037) (Figure 5A). The CC homozygotes also had a higher percentage of anaemia relative to children with CA or AA genotypes, but this difference was not statistically significant (9.3% vs. 2.2%, p = 0.11) (Figure 5B).

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