ArticleInfection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases2012
Genetic and functional evaluation of the role of DLL1 in susceptibility to visceral leishmaniasis in India.
Article in Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 21 citations in OpenAlex.
- Notch Ligand Delta-Like 1 Is Associated With Loss of Vascular Endothelial Barrier Function.Frontiers in physiology · 2021Article
- Delta-like 1 protein, vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis.Biomarkers in medicine · 2018Article
- Canine β-defensin-1 (CBD1) gene as a possible marker for Leishmania infantum infection in dogs.Parasites & vectors · 2017Article
- Expression of leukosialin (CD43) defines a major intrahepatic T cell subset associated with protective responses in visceral leishmaniasis.Parasites & vectors · 2015Article
- Lipoprotein lipase and PPAR alpha gene polymorphisms, increased very-low-density lipoprotein levels, and decreased high-density lipoprotein levels as risk markers for the development of visceral leishmaniasis by Leishmania infantum.Mediators of inflammation · 2014Article
- Visceral leishmaniasis: Clinical and demographic features in an African population.Pakistan journal of medical sciences · 2013Article
- Determinants for the development of visceral leishmaniasis disease.PLoS pathogens · 2013Review
- Resistance to visceral leishmaniasis is severely compromised in mice deficient of bradykinin B2-receptors.Parasites & vectors · 2012Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Chromosome 6q26-27 is linked to susceptibility to visceral leishmaniasis (VL) in Brazil and Sudan. DLL1 encoding the Delta-like 1 ligand for Notch 3 was implicated as the etiological gene. DLL1 belongs to the family of Notch ligands known to selectively drive antigen-specific CD4 T helper 1 cell responses, which are important in protective immune response in leishmaniasis. Here we provide further genetic and functional evidence that supports a role for DLL1 in a well-powered population-based study centred in the largest global focus of VL in India. Twenty-one single nucleotide polymorphisms (SNPs) at PHF10/C6orf70/DLL1/FAM120B/PSMB1/TBP were genotyped in 941 cases and 992 controls. Logistic regression analysis under an additive model showed association between VL and variants at DLL1 and FAM120B, with top associations (rs9460106, OR=1.17, 95%CI 1.01-1.35, P=0.033; rs2103816, OR=1.16, 95%CI 1.01-1.34, P=0.039) robust to analysis using caste as a covariate to take account of population substructure. Haplotype analysis taking population substructure into account identified a common 2-SNP risk haplotype (frequency 0.43; P=0.028) at FAM120B, while the most significant protective haplotype (frequency 0.18; P=0.007) was a 5-SNP haplotype across the interval 5' of both DLL1 (negative strand) and FAM120B (positive strand) and extending to intron 4 of DLL1. Quantitative RT/PCR was used to compare expression of 6q27 genes in paired pre- and post-treatment splenic aspirates from VL patients (N=19). DLL1 was the only gene to show differential expression that was higher (P<0.0001) in pre- compared to post-treatment samples, suggesting that regulation of gene expression was important in disease pathogenesis. This well-powered genetic and functional study in an Indian population provides evidence supporting DLL1 as the etiological gene contributing to susceptibility to VL at Chromosome 6q27, confirming the potential for polymorphism at DLL1 to act as a genetic risk factor across the epidemiological divides of geography and parasite species.
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