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)

A fundamental question for the intensivist is why some individuals but not others succumb to life-threatening infection. A growing body of evidence indicates that both the risk of acquiring infection and the risk of developing severe complications are determined by host genetic factors. These include a number of single gene defects with devastating consequences, e. g. interferon-gamma receptor mutations that lead to fatal infections with ubiquitous mycobacteria, but such examples are relatively rare. Of greater importance for routine clinical practice is the potentially vast number of genetic variants with subtle effects on the regulation or function of specific immunological, physiological and metabolic mediators. Such polygenic traits do not obey simple patterns of familial segregation seen for monogenic disorders, and their clinical investigation is further complicated by the environmental variability of infectious exposure. Recent advances in this field have therefore largely stemmed from hospital-based case-controlled studies that have uncovered disease associations with specific DNA polymorphisms in candidate gene regions. For example, tumour necrosis factor polymorphisms have been associated with susceptibility to malaria and other infections; chemokine receptor polymorphisms with susceptibility to HIV; natural resistance-associated macrophage protein 1 with tuberculosis; and mannose binding lectin polymorphisms with meningococcal disease. A much greater number of genetic associations will emerge as the full extent of human genomic diversity becomes known. The challenge for clinical investigators is to generate an epidemiological framework for population- and family-based association studies, which is sufficiently robust to exclude population artifacts and sufficiently powerful to be able to dissect true disease-causing polymorphisms from linked genetic markers. In the long term this approach promises to identify host mediators that are critical for pathogenesis and immunity and to yield molecular insights into the complex processes of human gene regulation. This information is likely to be of considerable value in designing more effective approaches to the treatment and prevention of life-threatening infectious disease.
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PMID:Genetic dissection of the molecular pathogenesis of severe infection. 1078 64

Several studies have focused their attention on the relationship between host genetic factors and susceptibility/resistance to severe malaria. However, there is a paucity of information concerning the role of host genetic factors in asymptomatic malaria, a form of low-grade Plasmodium falciparum infection without clinical symptoms. We investigated in this study the potential relationship between the host (human) genetic polymorphisms (glucose-6-phosphate dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor alpha [TNFalpha](-308) and (-238), and nitric oxide synthase 2 [NOS2](-954)) and the prevalence and profile of asymptomatic P. falciparum infection in 158 Gabonese schoolchildren. We found that G6PD A- heterozygous females (18 of 74) have a low prevalence of asymptomatic malaria (38.9% versus 67.3%; P = 0.03, by chi-square test). Children heterozygous for TNFalpha(-238) (25 of 156) carry high number of diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No statistically significant association was found between MBL, TNFalpha(-308), or NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on asymptomatic forms with those from the literature for others forms, we conclude that G6PD A- heterozygous females are protected against all forms of P. falciparum malaria, and that the TNFalpha(-238A) allele confers protection against clinical malaria.
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PMID:Human genetic polymorphisms and asymptomatic Plasmodium falciparum malaria in Gabonese schoolchildren. 1264 10