Human ADORA2A (Adenosine receptor A2a) ELISA Kit

In the erythrocytes, malaria parasite entry and infection is mediated through complex membrane sorting and signaling processes. We investigated the effects of single-locus and multilocus interactions to test the hypothesis that the members of the GPCR family genes, adenosine A2a receptor (ADORA2A) and G-protein coupled receptor kinase5 (GRK5), may contribute to the pathogenesis of malaria caused by Plasmodium falciparum (Pf) independently or through complex interactions. In a case-control study of adults, individuals affected by Pf malaria (complicated n = 168; uncomplicated n = 282) and healthy controls (n = 450) were tested for their association to four known SNPs in GRK5 (rs2230345, rs2275036, rs4752307 and rs11198918) and two in ADORA2A (rs9624472 and rs5751876) genes with malaria susceptibility, using techniques of polymerase chain reaction-restriction fragment length polymorphisms and direct DNA sequencing. Single-locus analysis showed significant association of 2 SNPs; rs5751876 (OR = 3.2(2.0-5.2); p = 0.0006) of ADORA2A and rs2230345 (OR = 0.3(0.2-0.5); p = 0.0006) of GRK5 with malaria. The mean of the serum creatinine levels were significantly higher in patients with variant GG (p = 0.006) of rs9624472 in ADORA2A gene compared to AA and AG genotypes in complicated Pf malaria cases, with the G allele also showing increased risk for malaria (OR = 1.3(1.1-1.6); p = 0.017). Analyses of predicted haplotypes of the two ADORA2A and the four GRK5 SNPs have identified the haplotypes that conferred risk as well as resistance to malaria with statistical significance. Molecular docking analysis of evolutionary rs2230345 SNP indicated a stable activity of GRK5 for the mutant allele compared to the wild type. Further, generalized multifactor dimensionality reduction to test the contribution of individual effects of the six polymorphisms and higher-order interactions to risk of symptoms/clinical complications of malaria suggested a best six-locus model showing statistical significance. The study provides evidence for the role of ADORA2A and GRK5 that might influence the etiology of malaria infection. (C) 2015 Elsevier B.V. All rights reserved.

APOE epsilon 4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and accounts for 50-65% of late-onset AD. Late-onset AD patients carrying or not carrying APOE epsilon 4 manifest many clinico-pathological distinctions. Thus, we applied a weighted gene co-expression network analysis to identify specific co-expression modules in AD based on APOE epsilon 4 stratification. Two specific modules were identified in AD APOE epsilon 4 carriers and one module was identified in non-carriers. The hub genes of one module of AD APOE epsilon 4 carriers were ISOC1, ENO3, GDF10, GNB3, XP04, ACLY and MATN2. The other module of AD APOE 4 carriers consisted of 10 hub genes including ANO3. ARPP21, HPC4 RASD2, PCP4 and ADORA2A. The module of AD APOE epsilon 4 non carriers consisted of 16 hub genes including DUSP5, TNERSF18, ZNF331, DNAJB5 and RIN1. The module of AD APOE epsilon 4 carriers including ISOC1 and ENO3 and the module of of the genes in the cluster of the ISOC1 and EN03 module of carriers was shown to be correlated in a time-dependent manner under APOE epsilon 4 treatment but not under APOE epsilon 3 treatment. In contrast, mRNA expression of the genes in the cluster of non-carriers' module was correlated under APOE epsilon 3 treatment but not under APOE epsilon 4 treatment. The modules of carriers demonstrated genetic bases and were mainly enriched in hereditary disorders and neurological diseases, energy metabolism-associated signaling and G protein-coupled receptor-associated pathways. The module including ISOC1 and ENO3 harbored two conserved promoter motifs in its hub gene cluster that could be regulated by common transcription factors and miRNAs. The module of non-carriers was mainly enriched in neurological, immunological and cardiovascular diseases and was correlated with Parkinson's disease. These data demonstrate that AD in APOE epsilon 4 carriers involves more genetic factors and particular biological processes, whereas AD in APOE epsilon 4 non carriers shares more common pathways with other types of diseases. The study reveals differential genetic bases and pathogenic and pathological processes between carriers and non-carriers, providing new insight into the mechanisms of the differences between APOE epsilon 4 carriers and non-carriers in AD.