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

Examination on G6PD deficiency in 349 patients of Shekii district hospital (Azerbaijan) revealed 16 hemi-, 4 homo- and 9 heterozygotic carriers of the defect. Gd- frequency, calculated from the data obtained (7.7%), may be compared to neighbouring regions' frequencies (6-30%). Carriers of G6PD deficiency are residents of 11 villages located in Alasani-Aphtalan valley, highly endemic with malaria in the past; nearly all marriages are endogamic. Physico-chemical and kinetic study of 10 mutant forms of G6PD, according to WHO program, led to identification of 5 variants of the II class (Shekii, Bideiz, Shirin-Bulakh, Okhut I and Zakataly) and 2 variants of the III class (Okhut II and Martinique-like). Resemblance of the majority of variants in electrophoretic mobility and the level of erythrocyte enzyme activity permit to suggest the existence of a common parental mutant G6PD allele distributed in this area.
 ...
PMID:[Genetic heterogeneity of G6PD deficiency: mutant alleles of G6PD in the Shekii district of Azerbaijan]. 14 81

The high frequencies of the Hb S and G6PD-deficiency genes in the tropics are explained by their relative resistance against malarial infection. They may confer advantage through lower infection rates or through lower parasitaemia. There is evidence that heterozygote carriers of these genes are partially protected. The mechanism of resistance is known for Hb S but not completely understood for the G6PD-deficiency gene. Other red cell factors are discussed with respect to innate resistance against malaria.
 ...
PMID:[Malaria hypothesis--the significance of the hereditary red cell traits Hb S and glucose-6-phosphate dehydrogenase deficiency in malaria (author's transl)]. 39 27

The jungle habitat of the Temuan aborigines harbors a variety of infectious diseases, the most notable being malaria. Our study of 15 genetic systems in the Temuan revealed substantial polymorphism and within-population genetic diversity. The polymorphisms for Hb beta, G6PD, and El are of interest in regard to genetic adaptation to malaria. Among the polymorphisms investigated we conclude that G6PD deficiency and elliptocytosis are likely to have malaria-resistant effects as evidenced by their low association with malarial parasitemia or their higher frequency in adults than in children. These findings suggest that the malarial habitat of the Temuans is livable in the long range sense for them because of the cluster of malaria-resistant alleles in their gene pool (G6PD)-, El, and possibly, but not tested here because of its low frequency, Hb beta E). The same condition probably holds for the Semai, the nearest aborigine neighbors of the Temuan (although the Semai have not been tested for malarial parasitemia and for these polymorphisms simultaneously), since the Semai have substantial Hb betaE, G6PD-, and El. The Temuan have a cultural identity system of rituals, beliefs, and certain aspects of language which effectively isolates them genetically from Malays and other nonaborigines. This system hinders the dilution of the malaria-resistant alleles of the Temuan gene pool with the malaria-susceptible alleles of the nonaborigine gene pools.
 ...
PMID:Genetic factors and malaria in the Temuan. 81 97

The frequency of PC allele for acid phosphatase in fourteen Sardinian villages correlates positively with the altitude and negatively with past malarial morbidity and GdMed prevalence. The susceptibility towards hemolytic favism in Sardinian males with G6PD deficiency is dependent on the erythrocyte acid phosphatase and thalassemia phenotypes. Thalassemia trait exerts a protective action only in subjects carrying PA allele for acid phosphatase. The data suggest that the gradient for malaria morbidity directly or indirectly, through interactions with thalassemia and G6PD polymorphisms, mediated by the habit of eating Vecia faba, may have had a significant role in determining the heterogeneous distribution of acid phosphatase polymorphism in Sardinia. Besides malaria, other environmental factors related with altitude seem to have been very important in shaping the present pattern of distribution of both acid phosphatase and G6PD polymorphisms in Sardinia.
 ...
PMID:Red cell acid phosphatase: another polymorphism correlated with Malaria? 118 Mar 55

The role of reactive oxygen species (ROS) generated by polymorphonuclear leucocytes (PMNs) in the host response against malaria was investigated. Non-activated human PMNs were added to cultures of P. falciparum in microtitre cells. Parasite viability was evaluated by the incorporation of radioactive hypoxanthine. Using PMN/RBC = 1/150 (starting parasitemia was 1%) the incorporation on the second day in culture was only 61% of the control cultures. An effect could be observed already after two hours of incubation (30% reduction at a 1/50 PMN/RBC ratio). A direct contact between the effector and target cells was obligatory for the expression of the damage. Parasites within G6PD-deficient erythrocytes were more sensitive to the PMNs than normal parasitized erythrocytes. This difference could be attributed to the production of reactive oxygen intermediates in the experimental system, since G6PD-deficient erythrocytes are generally more sensitive to oxidant stress. Salicylic acid was used as a scavenger and reporter molecule for hydroxyl radical fluxes. It is converted to the corresponding dihydroxybenzoic acid derivatives, which could be detected by HPLC. Uninfected NRBC or parasitized erythrocytes containing young ring forms could trigger the PMNs to produce much less ROS than the mature forms of the parasites. Other factors associated with PMNs may inactivate the parasites, such as phagocytosis, lysosomal enzymes or degradation toxic products of the PMNs. However our results indicate that increased oxidative stress induced by PMNs interfere with the growth of P. falciparum and could play a role in human evolution of abnormal erythrocytes.
 ...
PMID:Correlation between destruction of malarial parasites by polymorphonuclear leucocytes and oxidative stress. 133 29

With more than 300 different variants reported, the human enzyme glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is one of the most polymorphic proteins known. An estimated 400 million people throughout the world are deficient in G6PD; numerous lines of evidence indicate that this is because female heterozygotes have a selective advantage in malaria infections. The cloning of the G6PD gene has made it possible to clarify the molecular basis underlying this enzyme deficiency and polymorphism.
 ...
PMID:The molecular basis of glucose-6-phosphate dehydrogenase deficiency. 163 57

In an open clinical trial, thirty patients 14 to 44 years old and with acute uncomplicated falciparum malaria were given halofantrine hydrochloride 500 mg (2 tablets) 6-hourly for 3 doses, a total dose of 1500 mg. All 30 patients were cured, with a mean asexual parasite clearance time of 47.6 hours and mean fever clearance time of 36.6 hours. Post-dosing side-effects occurred in 6 patients consisting of mild to moderate headache, dizziness and abdominal muscle spasm. Drug-induced hemolysis did not occur in two G6PD deficient patients. Twenty-three out of 28 isolates tested (82%) were resistant to amodiaquine, 3 (11%) were resistant to the sulfadoxine-pyrimethamine combination, and all were sensitive to chloroquine, quinine and mefloquine by in vitro microtests. The study confirms the efficacy of halofantrine hydrochloride as a blood schizonticide in falciparum malaria.
 ...
PMID:Halofantrine in the treatment of acute uncomplicated falciparum malaria in the Philippines. 181 90

The human X chromosome-linked gene encoding glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is known to be highly polymorphic from the biochemical characterization of enzyme variants. The variant A (with enzyme activity in the normal range) and the variant A- (associated with enzyme deficiency) each have a frequency of about 0.2 in several African populations. Two restriction fragment length polymorphisms have also been found in people of African descent, but not in other populations, whereas a silent mutation has been shown to be polymorphic in Mediterranean, Middle Eastern, African, and Indian populations. We report now on two additional polymorphisms that we have detected by sequence analysis, one in intron 7 and one in intron 8. The analysis of 54 African male subjects for the seven polymorphic sites, clustered within 3 kilobases of the G6PD gene, has revealed only 7 of the 128 possible haplotypes, indicating marked linkage disequilibrium. These data have enabled us to suggest an evolutionary pathway for the different mutations, with only a single ambiguity. The mutation underlying the A variant is the most ancient and the mutation underlying the A- variant is the most recent. Since it seems reasonable that the A- allele is subject to positive selection by malaria, whereas the other alleles are neutral, G6PD may lend itself to the analysis of the role of random genetic drift and selection in determining allele frequencies within a single genetic locus in human populations.
 ...
PMID:Polymorphic sites in the African population detected by sequence analysis of the glucose-6-phosphate dehydrogenase gene outline the evolution of the variants A and A-. 192 16

We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of beta-thal, beta S, G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous alpha-/alpha-genotype and an overall alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with alpha-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the alpha-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.
 ...
PMID:Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population. 199 Aug 45

The study of inherited RBC resistance to malaria has increased our knowledge of the biochemistry and physiology of the host-parasite interaction and suggested potential sites for therapeutic intervention. Discovery by Jensen and Trager of the in vitro culture system for P falciparum has facilitated research in this area. Known RBC defects may affect invasion, growth, or merozoite liberation (Fig 1). Significant advances made in understanding mechanisms underlying protection against malaria should not obscure the fact that the data are far from complete. More knowledge is needed about the influence of the erythrocyte cytoskeleton on invasion and growth of parasites as well as the potential role of phospholipids, erythrocyte enzymes other than G6PD, or other metabolic products. Application of DNA analysis and recombinant technology may have an increasing impact on study of the interaction of RBC defects with malarial parasites.
 ...
PMID:Malaria and red cell genetic defects. 266 96


1 2 3 4 5 6 7 8 Next >>