Genetic and functional evaluation of the role of DLL1 in susceptibility to visceral leishmaniasis in India.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
Sanjana MehrotraJenefer M Blackwell

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 haplot...Continue Reading

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May 24, 2011·BMC Medical Genetics·Sanjana MehrotraJenefer M Blackwell

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Citations

Nov 16, 2012·Parasites & Vectors·Dirlei NicoClarisa Beatriz Palatnik-de-Sousa
Jan 10, 2013·PLoS Pathogens·Laura-Isobel McCallGreg Matlashewski
Aug 25, 2015·Parasitology International·Anshuman MishraKumarasamy Thangaraj
Apr 22, 2017·Parasites & Vectors·Lidiane Gomes da SilvaFilipe Dantas-Torres

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