Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10−04) and rs8099917 (P value = 5.5 × 10−04). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10−05). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10−04). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917

Human Red Cells With Paroxysmal Nocturnal Haemoglobinuria Phenotype Are Competent For The Growth Of Plasmodium falciparum

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired blood disorder characterised by acute intravascular haemolysis, due to increased susceptibility of red cells to complement -mediated lysis. Any red cell abnormality that would affect the invasion and growth of Plasmodium falciparum would serve as a useful tool for the future intervention of malaria infection in humans. The aim was to find out whether P. Falciparum can invade and infect these abnormal human red cells, and whether the parasite depends on the host cell for the synthesis of its GPI anchors. Patients with the PNH condition have a mixture of normal and abnormal red blood cells (RBCs) in their blood. In order to obtain a homogenous sample of abnormal (PNH) cells, PNH red cells were purified from patients with this condition by the process of 'panning'. The purified cells were used as hosts for the culture of P.falciparum in vitro. Results show that GPI-linked molecules on the red cell surface are not required for the efficient entry of the parasites, and that the PNH red cells are competent to sustain the growth of P.falciparum. Nigerian Quarterly Journal of Hospital Medicine Vol. 9, No. 2 (June 1999) pp. 138-14

2003 European society of hypertension - European Society of Cardiology guidelines for the management of arterial hypertension

status: publishe