Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between the malaria parasite and the human host involves a number of interactions that result in the parasite evading the human immune system. Since the stages of the malaria lifecycle are complex, this allows the use of various immune evasion strategies by the malaria parasite and has major implications in the development of a vaccine for malaria endemic areas. The present review highlights key host:parasite interactions. Plasmodia puts selection pressure on human gene frequencies, and studies into host genetic factors such as the Duffy blood group and sickle cell anaemia offer insight into the host- parasite relationship. In addition, parasite interactions with the different effector arms of the immune system can result in altered peptide ligand (APL) antagonism which alters the immune response from a pro- to an anti-inflammatory T cell response. Recent insights into the interaction between professional antigen presenting cells, dendritic cells (DCs), and malaria parasites is discussed in detail.
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PMID:Malaria parasite interactions with the human host. 1504 96

Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation.
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PMID:Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia. 2771 Dec 7