Limits...
Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis

View Article: PubMed Central - PubMed

ABSTRACT

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59–1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40–0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96–1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57–0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61–1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

No MeSH data available.


Related in: MedlinePlus

Meta-analysis forest plot for the association of G6PD with falciparum malaria.(Subgroup analysis by genotypes): homo/hemi or heterozygous). (a) Present the meta-analysis forest plot of the association of G6PD deficiency and falciparum malaria, grouped by genotypes. The heterozygous females were compared to a combined group comprising hemizygous males and homozygous female. There was a strong negative association between G6PD deficiency and malaria for the heterozygous. (b) Funnel plot of the heterozygous subgroup represents presence of publication bias towards negative association. (c) Trim and fill analysis indicate that the publication bias is too minimal to affect the significant negative association.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382680&req=5

f3: Meta-analysis forest plot for the association of G6PD with falciparum malaria.(Subgroup analysis by genotypes): homo/hemi or heterozygous). (a) Present the meta-analysis forest plot of the association of G6PD deficiency and falciparum malaria, grouped by genotypes. The heterozygous females were compared to a combined group comprising hemizygous males and homozygous female. There was a strong negative association between G6PD deficiency and malaria for the heterozygous. (b) Funnel plot of the heterozygous subgroup represents presence of publication bias towards negative association. (c) Trim and fill analysis indicate that the publication bias is too minimal to affect the significant negative association.

Mentions: Subgroup analysis was performed to identify the effect of population subgroups on the meta-analysis. We grouped data into genotypes by separately analyzing studies that reported different genotypes. When homo/hemizygous or heterozygous were analyzed separately, the outcome effect measures were significant for heterozygous (OR, 0.70; 95% CI, 0.57–0.87; n, 6; p = 0.001), but not for homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; n, 10; P = 0.10) indicating that the association is only present in heterozygous subgroup (Fig. 3a). However, there was a publication bias observed by funnel plot in favor of the protection (Fig. 3b). Trim and fill methods of Duval indicated that this publication bias is so minimal to affect the significant association in the heterozygous subgroup (OR, 0.71; 95% CI, 0.57–0.88; n, 7; P = 0.002) (Fig. 3c). Also, sensitivity analysis showed there was no single study effect on this association (Supplementary Table S4). Subgroup analysis by age revealed negative association with children only (OR, 0.72; 95% CI, 0.53–0.98; n, 9; P = 0.04) but not with children and adult subgroup (Supplementary Fig. S1). When the genders were analyzed separately, the significant association was only present with female subgroup (OR, 0.70; 95% CI, 0.50–0.98; n, 7; P = 0.04) (Supplementary Fig. S2). This corroborates the significant association for heterozygous subgroup since G6PD enzymopathy is sex-linked.


Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis
Meta-analysis forest plot for the association of G6PD with falciparum malaria.(Subgroup analysis by genotypes): homo/hemi or heterozygous). (a) Present the meta-analysis forest plot of the association of G6PD deficiency and falciparum malaria, grouped by genotypes. The heterozygous females were compared to a combined group comprising hemizygous males and homozygous female. There was a strong negative association between G6PD deficiency and malaria for the heterozygous. (b) Funnel plot of the heterozygous subgroup represents presence of publication bias towards negative association. (c) Trim and fill analysis indicate that the publication bias is too minimal to affect the significant negative association.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382680&req=5

f3: Meta-analysis forest plot for the association of G6PD with falciparum malaria.(Subgroup analysis by genotypes): homo/hemi or heterozygous). (a) Present the meta-analysis forest plot of the association of G6PD deficiency and falciparum malaria, grouped by genotypes. The heterozygous females were compared to a combined group comprising hemizygous males and homozygous female. There was a strong negative association between G6PD deficiency and malaria for the heterozygous. (b) Funnel plot of the heterozygous subgroup represents presence of publication bias towards negative association. (c) Trim and fill analysis indicate that the publication bias is too minimal to affect the significant negative association.
Mentions: Subgroup analysis was performed to identify the effect of population subgroups on the meta-analysis. We grouped data into genotypes by separately analyzing studies that reported different genotypes. When homo/hemizygous or heterozygous were analyzed separately, the outcome effect measures were significant for heterozygous (OR, 0.70; 95% CI, 0.57–0.87; n, 6; p = 0.001), but not for homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; n, 10; P = 0.10) indicating that the association is only present in heterozygous subgroup (Fig. 3a). However, there was a publication bias observed by funnel plot in favor of the protection (Fig. 3b). Trim and fill methods of Duval indicated that this publication bias is so minimal to affect the significant association in the heterozygous subgroup (OR, 0.71; 95% CI, 0.57–0.88; n, 7; P = 0.002) (Fig. 3c). Also, sensitivity analysis showed there was no single study effect on this association (Supplementary Table S4). Subgroup analysis by age revealed negative association with children only (OR, 0.72; 95% CI, 0.53–0.98; n, 9; P = 0.04) but not with children and adult subgroup (Supplementary Fig. S1). When the genders were analyzed separately, the significant association was only present with female subgroup (OR, 0.70; 95% CI, 0.50–0.98; n, 7; P = 0.04) (Supplementary Fig. S2). This corroborates the significant association for heterozygous subgroup since G6PD enzymopathy is sex-linked.

View Article: PubMed Central - PubMed

ABSTRACT

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59–1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40–0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96–1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57–0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46–1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61–1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

No MeSH data available.


Related in: MedlinePlus