An Expression Quantitative Trait Locus of Fc Gamma Receptor Genes is Associated with Anti-Malarial IgG Responses and Infection Levels in Burkinabe Families.

Background: The interaction between antibodies and Fc gamma receptors (FcγRs) plays a critical role in regulating immune responses to Plasmodium falciparum. Polymorphisms in genes encoding FcγRs influence the host's capacity to control parasite infection. This study investigates whether non-coding variants influencing FcγR expression are associated with anti-malarial immunization and infection traits.

From Genome-wide Association Studies to Functional Variants: ARL14 Cis-regulatory Variants Are Associated With Severe Malaria.

Background: Genome-wide association studies have identified several nonfunctional tag single-nucleotide polymorphisms (SNPs) associated with severe malaria. We hypothesized that causal SNPs could play a significant role in severe malaria by altering promoter or enhancer activity. Here, we sought to identify such regulatory SNPs.

A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Infection in Children Residing in Burkina Faso.

Antibodies play a crucial role in activating protective immunity against malaria by interacting with Fc-gamma receptors (FcγRs). Genetic variations in genes encoding FcγRs can affect immune cell responses to the parasite. In this study, our aim was to investigate whether non-coding variants that regulate FcγR expression could influence the prevalence of infection.

Short tandem repeats are important contributors to silencer elements in T cells.

The action of cis-regulatory elements with either activation or repression functions underpins the precise regulation of gene expression during normal development and cell differentiation. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts. In sharp contrast, gene repression by cis-acting silencers, defined as genetic elements that negatively regulate gene transcription in a position-independent fashion, is less well understood.

ATP2B4 regulatory genetic variants are associated with mild malaria.

Background: Genome-wide association studies have identified ATP2B4 as a severe malaria resistance gene. Recently, 8 potential causal regulatory variants have been shown to be associated with severe malaria.

Methods: Genotyping of rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452 was performed in 154 unrelated individuals (79 controls and 75 mild malaria patients).

Identification of Regulatory Element Containing Functional Genetic Variants Associated with Severe Malaria.

Genome-wide association studies for severe malaria (SM) have identified 30 genetic variants mostly located in non-coding regions. Here, we aimed to identify potential causal genetic variants located in these loci and demonstrate their functional activity. We systematically investigated the regulatory effect of the SNPs in linkage disequilibrium (LD) with the malaria-associated genetic variants.

Female hormones prevent sepsis-induced cardiac dysfunction: an experimental randomized study.

Although epidemiologic research has demonstrated significant differences in incidence and outcomes of sepsis according to sex, their underlying biological mechanisms are poorly understood. Here, we studied the influence of hormonal status by comparing in vivo cardiac performances measured by MRI in non-ovariectomized and ovariectomized septic female rats. Control and ovariectomized rats were randomly allocated to the following groups: sham, sepsis and sepsis plus landiolol.

Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy.

Infection by the protozoan causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction.

Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease.

Unlabelled: Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)).