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Polymorphisms in the Gene That Encodes the Iron Transport Protein Ferroportin 1 Influence Susceptibility to Tuberculosis
Background: We studied the association between iron intake and polymorphisms in the iron transporter gene, SLC40A1, and the risk of tuberculosis. Methods: We compared iron intake, the frequency of SLC40A1 mutations, and interactions between these variables among 98 TB patients and 125 controls in Kwazulu-Natal, South Africa. Results: Four SLC40A1 SNPs were associated with an increased risk of tuberculosis and one with reduced risk. We also found a gene-environment interaction for four non-exonic SNPs and iron intake. Conclusions: This pilot study demonstrated an association between polymorphisms in SLC40A1 and tuberculosis and provided evidence for an interaction between dietary iron and SLC40A1.Organismic and Evolutionary Biolog
Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever
Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis