Glucose-6-Phosphate-Dehydrogenase Deficiency, Sickling, and Malaria in African Children in South Western Nigeria

Gilles, H. M.; Fletcher, K. A.; Hendrickse, R. G.; Lindner, Robert; Reddy, S.; Allan, N. C.

doi:10.1016/s0140-6736(67)91037-9

Cited by 128 publications

(71 citation statements)

References 14 publications

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“…1 More recently, the HbC mutation (b6Glu4Lys, rs33930165) has been associated with protection from severe malaria in Mali, Ghana and Burkina Faso, [2][3][4] although initial studies indicated lack of protection in Nigeria and in Mali. 5,6 Modiano et al 4 detected a 29% reduction in risk of clinical malaria in HbAC individuals, and a 93% reduction in risk of clinical malaria in HbCC individuals in a large population living in Burkina faso; this study provided evidence of protective effect against both mild and severe malaria. In the same way, we found that HbC carriers had less frequent mild malaria attacks than AA individuals in the same age group in a longitudinal study of individuals living in Burkina Faso, and that HbC was negatively associated with mild malaria and maximum parasitemia by using family-based association tests.…”

Section: Introductionsupporting

confidence: 53%

Evidence for epistasis between hemoglobin C and immune genes in human P. falciparum malaria: a family study in Burkina Faso

et al. 2011

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Hemoglobin C (HbC) has been recently associated with protection against Plasmodium falciparum malaria. It is thought that HbC influences the development of immune responses against malaria, suggesting that the variation at the HbC locus (rs33930165) may interact with polymorphic sites in immune genes. We investigated, in 198 individuals belonging to 34 families living in Burkina Faso, statistical interactions between HbC and 11 polymorphisms within interleukin-4 (IL4), IL12B, NCR3, tumor necrosis factor (TNF) and lymphotoxin-a (LTA), which have been previously associated with malaria-related phenotypes. We searched for multilocus interactions by using the pedigree-based generalized multifactor dimensionality reduction approach. We detected 29 multilocus interactions for mild malaria, maximum parasitemia or asymptomatic parasitemia after correcting for multiple tests. All the single-nucleotide polymorphisms studied are included in several multilocus models. Nevertheless, most of the significant multilocus models included IL12B 3 0 untranslated region, IL12Bpro or LTA þ 80, suggesting that those polymorphisms play a particular role in the interactions detected. Moreover, we identified six multilocus models involving NCR3 that encodes the activating natural killer (NK) receptor NKp30, suggesting an interaction between HbC and genes involved in the activation of NK cells. More generally, our findings suggest an interaction between HbC and genes influencing the activation of effector cells for phenotypes related to mild malaria.

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Section: Introductionsupporting

confidence: 53%

Evidence for epistasis between hemoglobin C and immune genes in human P. falciparum malaria: a family study in Burkina Faso

et al. 2011

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“…This strongly supports the malaria hypothesis. [27][28][29][30][31] In conclusion, G6PD deficiency occurs frequently in several areas of Saudi Arabia, and G6PD-Mediterranean is the most frequently encountered variant producing severe G6PD deficiency. The frequency correlates with malaria endemicity, and thus it may provide a natural protection against malaria, as is the situation in several populations of the world where sickle cell gene (HbS), α-and β-thalassemias and G6PD deficiency provide a strong inborn resistance against malaria.…”

Section: Discussionmentioning

confidence: 99%

G6PD Deficiency, Distribution and Variants in Saudi Arabia: An Overview

Warsy

El‐Hazmi

2001

Annals of Saudi Medicine

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Background:The first report of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Saudi population of the Eastern Province paved the way for extensive investigations to determine the distribution and molecular pathogenesis of G6PD deficiency in Saudis in different parts of the country. Materials and Methods: During a national study lasting from 1982 to 1993, 24,407 Saudis in 31 different areas of Saudi Arabia were screened for G6PD deficiency using spectrophoretic estimation of the enzyme activity and electrophoretic separation of the phenotypes. Results:The results in the males and females were separately analyzed, and showed a statistically significant difference in the frequency in the male (0.0905) and female (0.041) population (P<0.05). The frequency in the male varied from 0 to 0.398, and in the female from 0 to 0.214. The phenotypes identified included G6PD-A

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“…20,21 Since the mortality from falciparum malaria was related to parasite densities, 22 these children had a lower mortality rate from malaria. [23][24][25][26] Similar protection is provided by the G-6-PD deficiency, 27,28 and thus an increased frequency of these genes is encountered in most of the areas of the world that are or have been malaria endemic.…”

mentioning

confidence: 99%

“…7,[10][11][12][13] Thus it may be stated that the malaria hypothesis is applicable in Saudi Arabia as in other populations of the world. 18,19,[24][25][26][27][28] Control of malaria in an area is believed to result in decrease in the frequency of these genes, though it may require several generations or several hundred years before the frequency is decreased. 18,29 It is thus necessary to control malaria in areas which have a history of malaria endemicity and this will have benefit to the future generations, which may develop a lower frequency of the genetic blood diseases.…”

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confidence: 99%

The Frequency of Glucose-6-Phosphate Dehydrogenase Phenotypes and Sickle Cell Genes in Al-Qatif Oasis

El‐Hazmi¹,

Warsy²

1994

Annals of Saudi Medicine

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Glucose-6-Phosphate-Dehydrogenase Deficiency, Sickling, and Malaria in African Children in South Western Nigeria

Cited by 128 publications

References 14 publications

Evidence for epistasis between hemoglobin C and immune genes in human P. falciparum malaria: a family study in Burkina Faso

Evidence for epistasis between hemoglobin C and immune genes in human P. falciparum malaria: a family study in Burkina Faso

G6PD Deficiency, Distribution and Variants in Saudi Arabia: An Overview

The Frequency of Glucose-6-Phosphate Dehydrogenase Phenotypes and Sickle Cell Genes in Al-Qatif Oasis

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