Background: Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM.
Methodology/principal Findings: The RNASE3 gene and flanking regions were sequenced in 206 Ghanaian children enrolled in a hospital based malaria study. An association study was carried out to assess the significance of five SNPs in CM (n=45) and SA (n=56) cases, respectively. The two severe case groups (CM and SA) were compared with the non-severe control group comprising children suffering from UM (n=105). The 371G allele was significantly associated with CM (p=0.00945, OR=2.29, 95% CI=1.22-4.32) but not with SA. Linkage disequilibrium analysis demonstrated significant linkage between three SNPs and the haplotype combination 371G/*16G/*94A was strongly associated with susceptibility to CM (p=0.000913, OR=4.14, 95% CI=1.79-9.56), thus, defining a risk haplotype. The RNASE3 371GG genotype was found to be under frequency-dependent selection.
Conclusions/significance: The 371G allele of RNASE3 is associated with susceptibility to CM and forms part of a risk associated haplotype GGA defined by the markers: rs2073342 (G-allele), rs2233860 (G-allele) and rs8019343 (A-allele) respectively. Collectively, these results suggest a hitherto unrecognized role for eosinophils in CM pathogenesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246477 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029465 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Macrolide resistance due to (55).
Microbiol Spectr
January 2025
Institute for Microbial Systems and Society, Faculty of Science, University of Regina, Regina, Saskatchewan, Canada.
Unlabelled: Antimicrobial resistance (AMR) is a global threat. The identification and characterization of novel resistance genes is integral to AMR surveillance. The (55) gene was originally identified through whole genome sequencing of macrolide-resistant strains of .
View Article and Find Full Text PDFcolonization is not mediated by bile salts and utilizes Stickland fermentation of proline in an model.
mSphere
January 2025
Department of Food Science and Technology and Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Treatment with antibiotics is a major risk factor for infection, likely due to depletion of the gastrointestinal microbiota. Two microbiota-mediated mechanisms thought to limit colonization include the conversion of conjugated primary bile salts into secondary bile salts toxic to growth and competition between the microbiota and for limiting nutrients. Using a continuous flow model that simulates the nutrient conditions of the distal colon, we investigated how treatment with 6 clinically used antibiotics influenced susceptibility to infection in 12 different microbial communities cultivated from healthy individuals.
View Article and Find Full Text PDFPaddlewheel-type and half-paddlewheel-type diruthenium(II,II) complexes with 1,8-naphthyridine-2-carboxylate.
Dalton Trans
January 2025
Department of Chemistry, Graduate School of Natural Science and Technology, Shimane University, 1060, Nishikawatsu, Matsue, Shimane, 690-8504, Japan.
Paddlewheel-type diruthenium(II,II) complexes are paramagnetic with two unpaired electrons ( = 1) and can be utilized as versatile building blocks for higher-order structures, such as supramolecular complexes, coordination polymers, and metal-organic frameworks, although they are generally highly air-sensitive. In this study, we developed an air-stable paddlewheel-type diruthenium(II,II) complex with two electron-withdrawing 1,8-naphthyridine-2-carboxylate (npc) ligands, [Ru(μ-npc)(OCMe)] (1). The two acetate ligands in 1 can be replaced by other carboxylate ligands; the solvothermal reactions of 1 with benzoic acid (HOCPh) yields the heteroleptic [Ru(μ-npc)(OCPh)] (2), whereas its reaction with 1,8-naphthyridine-2-carboxylic acid (Hnpc) produces the homoleptic [Ru(μ-npc)(η-npc)] (3).
View Article and Find Full Text PDFRare and common genetic variants underlying the risk of Hirschsprung's disease.
Hum Mol Genet
January 2025
Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei 430030, China.
Hirschsprung's disease (HSCR) is a congenital enteric neuropathic disorder characterized by high heritability (>80%) and polygenic inheritance (>20 genes). The previous genome-wide association studies (GWAS) identified several common variants associated with HSCR and demonstrated increased predictive performance for HSCR risk in Europeans using a genetic risk score, there remains a notable gap in knowledge regarding Chinese populations. We conducted whole exome sequencing in a HSCR case cohort in Chinese.
View Article and Find Full Text PDFDeciphering the Role of Calcium Signaling Pathway-Associated Single Nucleotide Variants in Susceptibility to Hypertension.
J Clin Lab Anal
January 2025
Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Background: As a complex disease, hypertension (HTN) is influenced by both genetic and environmental factors and their interaction. The calcium signaling pathway is known to be involved in the regulation of blood pressure, and dysfunction in this pathway may contribute to the development of hypertension. Genome-wide association studies (GWAS) have identified several genes in the calcium signaling pathway associated with susceptibility to HTN, including PLCB1, ATP2B1, and ADRB1.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!