Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In studying the relationship between genetic abnormalities of red blood cells and malaria endemicity in the Vanuatu archipelago in the southwestern Pacific, we have found that of 1,442 males tested, 98 (6.8%) were G6PD deficient. The prevalence of GdPD deficiency varied widely (0%-39%), both from one island to another and in different parts of the same island, and generally correlated positively with the degree of malaria transmission. The properties of G6PD from GdPD-deficient subjects were analyzed in a subset of 53 samples. In all cases the residual red-blood-cell activity was < 10%. There were three phenotypic patterns. PCR amplification and sequencing of the entire coding region of the G6PD gene showed that the first of these patterns corresponded to G6PD Union (nucleotide 1360C-->T; amino acid 454Arg-->Cys), previously encountered elsewhere. Analysis of samples exhibiting the second pattern revealed two new mutants: G6PD Vanua Lava (nucleotide 383T-->C; amino acid 128Leu-->Pro) and G6PD Namoru (nucleotide 208T-->C; amino acid 70Tyr-->His); in three samples, the underlying mutation has not yet been identified. Analysis of the sample exhibiting the third pattern revealed another new mutant: G6PD Naone (nucleotide 497G-->A; amino acid 166Arg-->His). Of the four mutations, G6PD Union and G6PD Vanua Lava have a polymorphic frequency in more than one island; and G6PD Vanua Lava has also been detected in a sample from Papua New Guinea. G6PD deficiency is of clinical importance in Vanuatu because it is a cause of neonatal jaundice and is responsible for numerous episodes of drug-induced acute hemolytic anemia.
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PMID:Multiple glucose 6-phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (southwestern Pacific). 782 90

To assess natural immunity against the circumsporozoite (CS) protein and the synthetic vaccine SPf66, immunologic studies were carried out in a highly endemic malarious area of Papua New Guinea. Antibody prevalence, antibody titers, and T cell proliferation against both antigens were measured in 214 adults. Immunologic data were analyzed with respect to longitudinal malariologic and morbidity data. Evidence of genetic traits such as glucose-6-phosphate dehydrogenase deficiency and ovalocytosis was analyzed. Antibody prevalence was high, with 79% and 84% for CS protein and SPf66, respectively, while T cell proliferation was infrequent and low, with 14% and 12% responders, respectively. Anti-CS protein antibodies increased with age but showed no association to malaria indices or morbidity. No protective value was observed with T cell responses or with humoral response to SPf66. These results provide a first description of naturally developed immunity against SPf66 and suggest further studies in to fully understand the mechanism of immunity against this antigen.
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PMID:Assessment of the humoral and cell-mediated immunity against the Plasmodium falciparum vaccine candidates circumsporozoite protein and SPf66 in adults living in highly endemic malarious areas of Papua New Guinea. 794 57

It seems that thalassemia and/or hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency (G-6-PD) have some protective effects against malaria infection. To verify this, hemoglobin typing and methehoglobin reduction test were performed on 115 malaria patients and compared with controls. It was found that the number of thalassemia/hemoglobinopathies in the malaria group and in the control group were not significantly different and also occurrence of G-6-PD deficiency in the malaria group was not different from that of the controls. Clinical manifestations of malaria in any group are quite similar. It is concluded that there is no protective effect against malaria in thalassemia/hemoglobinopathies or G-6-PD deficiency.
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PMID:Prevalences of thalassemia/hemoglobinopathies and G-6-PD deficiency in malaria patients. 796 25

There is a high prevalence of a familial flavin-deficient red blood cell in Ferrara province in the Po delta in northern Italy, believed to have been selected for by malaria which was endemic from the 12th century. In the present study, activities of FAD-dependent red-cell glutathione reductase (EGR) in the Grosseto area of Maremma on the west coast of Italy where malaria was endemic from 300 B.C. are compared both with activities in the Ferrara area and with activities where there was no history of endemic malaria--in the Florence area and in London in people of Anglo-Saxon origin. EGR activities were similar in Grosseto and Ferrara and were significantly lower than in Florence and London. As previously found in Ferrara, low EGR activity in Grosseto was shown to be unrelated to low dietary riboflavin intake. These findings in Grosseto, suggesting selection by malaria, are particularly interesting because, unlike the situation in Ferrara and most other malarial areas, the prevalence of thalassemia and glucose-6-phosphate dehydrogenase deficiency is very low, and they do not appear to have been selected for in Maremma. It is possible that a flavin-deficient red cell, known to inhibit growth of the malaria parasite, was an important protecting factor in the population of this area over the centuries.
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PMID:Is the flavin-deficient red blood cell common in Maremma, Italy, an important defense against malaria in this area? 797 61

Women's fertility, gathered from the 1961 Italian population census, and estimates of heterozygote frequencies for thalassemia and G6PD deficiency (Siniscalco et al. 1961, 1966) in 52 Sardinian villages were examined to study at the population level the mechanisms that have maintained the stability of these polymorphisms over long periods. Sardinian villages were classified according to low or high frequency of heterozygotes, and the reproductive behavior of the women living in these areas was analyzed. A high mean number of children per woman and a low percentage of women without children with a high heterozygote frequency was demonstrated. The observed differential fertility and sterility were interpreted as being the result of different numeric ratios within each area between normal homozygous and heterozygous women, who were less and more resistant, respectively, to malarial infection, according to Haldane's theory. The effect of differing degrees of malaria on fertility rates has been demonstrated previously (Zei et al. 1990). To account for the effect of the genetic and epidemiological composition of an area on reproductive behavior, we classified data on women's fertility and sterility by heterozygote frequency level and malarial morbidity level. A combined and direct effect of inherited and acquired immunities on fertility and sterility rates was shown. The level of endemicity in an area may contribute to decreasing or increasing fitness, which is already influenced by the stable balanced polymorphisms.
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PMID:Differential fertility as a mechanism maintaining balanced polymorphisms in Sardinia. 808 54

The frequencies of four malaria associated erythrocyte genetic abnormalities have been established in 1000 Omani subjects. They are: homozygous alpha+ thalassaemia (-alpha/-alpha) 0.45; high Hb A2 beta thalassaemia trait 0.015; sickle trait (Hb A/S) 0.061; and glucose 6 phosphate dehydrogenase deficiency (Gd-): males 0.27, females 0.11. From our data the alpha+ (-alpha/) thal gene (confirmed by Southern blotting) is pandemic in this population. Moreover, in spite of the very high frequency of Gd-, oxidative haemolytic syndromes are very uncommon. Also preliminary data indicate that among the Omani population with sickle cell disease, homozygosity of the alpha+ gene markedly modifies the clinical picture.
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PMID:Frequency and clinical significance of erythrocyte genetic abnormalities in Omanis. 832 Jul 2

G6PD deficiency has been studied in two tribal populations: Kissan tribals of Orissa and Kannikar tribals of Nedumungad Taluk, Trivandrum, Kerala. The percentage frequencies of G6PD deficiency are 14.13% and 5.5%, respectively. The two areas have a different pattern with respect to malarial infection. The Orissa one is an endemic malaria zone, while the Kerala one is less malarious. This is very well reflected by the frequency distribution of G6PD deficiency.
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PMID:Study of glucose-6-phosphate dehydrogenase (G6PD) in the Kissan tribals of Orissa and the Kannikar tribals of Kerala, India. 833 38

Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is usually found at high frequencies in areas of the world where malaria has been endemic. The frequency and genetic basis of G6PD deficiency have been studied in Africa, around the Mediterranean, and in the Far East, but little such information is available about the situation in India. To determine the extent of heterogeneity of G6PD, we have studied several different Indian populations by screening for G6PD deficiency, followed by molecular analysis of deficient alleles. The frequency of G6PD deficiency varies between 3% and 15% in different tribal and urban groups. Remarkably, a previously unreported deficient variant, G6PD Orissa (44 Ala-->Gly), is responsible for most of the G6PD deficiency in tribal Indian populations but is not found in urban populations, where most of the G6PD deficiency is due to the G6PD Mediterranean (188 Ser-->Phe) variant. The KmNADP of G6PD Orissa is fivefold higher than that of the normal enzyme. This may be due to the fact that the alanine residue that is replaced by glycine is part of a putative coenzyme-binding site.
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PMID:A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44 Ala-->Gly), is the major polymorphic variant in tribal populations in India. 853 62

The balanced polymorphism of glucose-6-phosphate dehydrogenase deficiency (G6PD-) is believed to have evolved through the selective pressure of malarial combined with consumption of fava beans. The implicated fava bean constituents are the hydroxypyrimidine glucosides vicine and convicine, which upon hydrolysis of their beta-O-glucosidic bond, became protein pro-oxidants. In this work we show that the glucosides inhibit the growth of Plasmodium falciparum, increase the hexose-monophosphate shunt activity and the phagocytosis of malaria-infected erythrocytes. These activities are exacerbated in the presence of beta-glucosidase, implicating their pro-oxidant aglycones in the toxic effect, and are more pronounced in infected G6PD- erythrocytes. These results suggest that G6PD- infected erythrocytes are more susceptible to phagocytic cells, and that fava bean pro-oxidants are more efficiently suppressing parasite propagation in G6PD- erythrocytes, either by directly affecting parasite growth, or by means of enhanced phagocytic elimination of infected cells. The present findings could account for the relative resistance of G6PD- bearers to falciparum malaria, and establish a link between dietary habits and malaria in the selection of the G6PD- genotype.
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PMID:Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria: effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells. 871 Apr 17

We review here some recent data about glucose-6-phosphate dehydrogenase (G6PD), the first and key regulatory enzyme of the pentose phosphate pathway. New evidence has been presented to suggest that malaria is a selective agent for G6PD deficiency, which is the most common enzymopathy in man, and that G6PD deficiency, generally considered to be a mild and benign condition, is significantly disadvantageous in certain environmental conditions. At the molecular level, the enzyme structure has recently been elucidated and mechanisms regulating G6PD gene expression have been determined. A G6PD knock-out mutation introduced in mouse cells makes them exquisitely sensitive to oxidative stress, indicating that this ubiquitous metabolic enzyme has a major role in the defence against oxidative stress, even in eukaryotic nucleated cells, which have several alternative routes for providing the same protection. Because of the high prevalence of G6PD deficiency in many populations, it is expected that these findings will prompt further studies to ascertain the putative role of G6PD deficiency in conditions such as carcinogenesis and ageing.
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PMID:A new lease of life for an old enzyme. 876 Mar 36


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