Interferon-induced protein with tetratricopeptide repeats 1(IFIT1) polymorphism as a genetic marker of cerebral malaria in Thai population

Objective:To know whether the effect of interferon-induced protein with tetratricopeptide repeats(IFIT)1 polymorphism influences the susceptibility of cerebral malaria outcome.Methods:Case-control association study was performed among 314 Thai patients(110 with cerebral malaria and 204 with uncomplicated malaria)infected with Plasmodium falciparum.Genotyping for five tag-single nucleotide polymorphisms of IFIT1 was performed by endpoint genotyping.Results:Genotype frequencies of all tag-SNPs(single nucleotide polymorphisms)showed no association with malaria outcome.However,C allele of rs11203109 was associated with the protection from cerebral malaria(OR=0.62,95%CI=0.38-0.99,P=0.048).Two single nucleotide polymorphisms(rs5786868 and rs57941432)were in linkage disequilibrium with rs11203109.Conclusions:This suggests that our associated single nucleotide polymorphism(rs11203109)might be a genetic marker of cerebral malaria progression in the Thai population.

Iron dysregulation in beta-thalassemia

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide.Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron.The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis.Ferroportin is the sole cellular iron export protein,and its expression is regulated transcriptionally,post-transcriptionally and posttranslationally.Hepcidin,a hormone produced by liver cells,post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes.Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in betathalassemia patients.Beta-thalassemia patients show marked hepcidin suppression,ineffective eiythropoiesis,anemia and iron overload.Beta-thalassemia is common in the Mediterranean region,Southeast Asia and the Indian subcontinent,and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease.Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.

Comparative genome analysis between Southeast Asian and South American Zika viruses

Objective:To understand the cause for the differences between potentially mild Southeast Asian and the more pathogenic ZIKV in South America.Methods:A comparative genomic analysis was performed to determine putative causations stemming from ZIKV.Results:Phylogcnctic analyses integrating geographical and time factors revealed that Southeast Asian ZIKV might not be the direct source of South American outbreaks as previously speculated.Amino acid residues unique to South American ZIKV isolates at the envelope,pr and NS1 proteins are listed and shown in the structural context.These unique residues on external viral proteins are not found in Southeast Asian ZIKV and could be responsible for the ongoing outbreak either via an intrinsic property of the virus or interactions with human immunity.Only a selected few primer/probe sets currently in clinical use were identified of being capable of detecting ZIKV strains worldwide.The envelope proteins of dengue virus(DENV) and ZIKV also showed a remarkable degree of similarity especially at the surface residues.Conclusions:findings that may help explain the cross-reactivity of DENV antibodies to ZIKV.Thus,major caveats must be exercised in using existing diagnostic tools for ZIKV.