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)

The importance of innate immunity in malaria has been suggested for early protection from maturation and multiplication of Plasmodium parasites injected via infected mosquitoes. In this study, the killer cell immunoglobulin-like receptor (KIR) genes in innate immunity were investigated for an association with malaria in the comparison between Plasmodium-positive and Plasmodium-negative Melanesian individuals in the Solomon Islands, one of the most hyperendemic malaria regions in the world. The higher frequency of a pair of KIR3DL1 and KIR2DS4 was observed in the Plasmodium-positive individuals, which led to the investigation of KIR3DL1/S1 genotypes in concert with KIR2DS4 allelic variants. The positive individuals showed the highest frequency of KIR3DL1/KIR3DS1 heterozygosity, which might suggest the masking of activating KIR3DS1 by inhibitory KIR3DL1 at allelic levels to maintain the KIR3DS1-driven activation of natural killer cells diminished in controlling Plasmodium proliferation. The extended analysis with A/B genotypes further revealed the trend of parasitic positive individuals to be KIR3DL1/KIR3DS1 heterozygous in pair with KIR2DS4 nondeleted variants in a set of KIR genes inheritable as the AB genotypes. To the best of our knowledge, this study is the first KIR investigation of the malaria-infected population, which strengthened the potential associations of KIR with malaria pathogenesis. The balance of inhibitory and activating KIR3D genes (KIR3DL1/S1) and membrane-bound or secreted status of KIR2DS4 alleles in the interaction with the other KIR genes in the AB genotypes might constitute a part of KIR characteristics to determine resistance or susceptibility to Plasmodium parasitic infection.
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PMID:KIR3DL1/S1 genotypes and KIR2DS4 allelic variants in the AB KIR genotypes are associated with Plasmodium-positive individuals in malaria infection. 1985 4

Receptors encoded within the Natural Killer Cell (NKC) complex and Killer Immunoglobulin like (KIRs) genomic regions have been suggested to influence malaria pathogenesis and infection susceptibility. We have examined KIR locus in relation to risk of infection and disease in Tea tribes (TT) of Austro Asiatic affinity and Tibeto-Burman (TB) populations from malaria endemic regions of Assam. Consistent with differences in their genetic background, KIR gene loci frequencies differed in studied groups. Surprisingly, KIR3DS1 frequency in TT was low (17%) and comparable to that reported from African populations. KIR3DL1 frequency was positively associated with malaria severity (Pearson phi, R(2) = 0.297 p = 0.006) and logistic regression modelling predicted KIR3DL1 as a risk factor in complicated malaria [Odds Ratio (95% C.I)] = [6.39 (1.34-30.60)]. An interaction between ethnicity and KIR3DL1 was also seen where higher proportion of KIR3DL1 positive and complicated malaria patients belonged to Tea tribes (p = 0.009). Notably, four activating genes protected from frequent malaria (p = 0.02) while six activating genes enhanced the risk of complicated malaria (p = 0.05). Combination of KIR2DS4, KIR2DS4del, KIR2DS5 negatively influenced disease outcome in Tea tribes (p = 0.048) but not in Tibeto-Burman. In conclusion our data indicates KIR gene loci differentially influenced malaria outcome in Tea tribes and Tibeto-Burman and that four activating genes appeared to provide optimal activation that protected from frequent episodes of malaria. Our data also indicated KIR3DS1 to be an ancestral genotype, maintained at low frequency possibly by malaria in the Austro Asiatic tribes.
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PMID:Differential association of KIR gene loci to risk of malaria in ethnic groups of Assam, Northeast India. 2188 18