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A Single Haplotype of IFNG Correlating With Low Circulating Levels of Interferon-γ Is Associated With Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis
- Source :
- Clinical Infectious Diseases. 71:274-281
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Background Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop the disease. This suggest that host genetics may play a role in this response. We investigated whether single nucleotide polymorphisms (SNPs) in IFNG may be associated with elevated or decrease risk in the development of cutaneous leishmaniasis (CL). Methods We assessed 9 SNP and cytosine-adenine (CA) repeats in IFNG by nucleotide sequencing in 647 patients with CL caused by Leishmania guyanensis and 629 controls. Circulating plasma IFN-γ levels were also assayed in 400 patients with CL and 400 controls. Results The rs2069705TT genotype is associated with elevated risk of developing CL compared with the rs2069705CC genotype (OR, 1.7; 95% CI, 1.3–2.4; P = .0008). There is a 70% chance that this genotype raises the risk of developing CL. In a dominant model, carriers of the rs2069705T allele compared with the rs2069705CC genotype showed a 50% (range, 20–100%) increased risk of developing CL (OR, 1.5; 95% CI, 1.2–2.0; P = .0004). Haplotype analysis showed 1 haplotype (H1) associated with low levels of IFN-γ presented an increased risk of 60% of developing CL (OR, 1.6; 95% CI, 1.3–1.9; P = 5 × 10−5) compared with non-H1. Conclusions IFNG variant rs2069705 seems to be a genetic modifier of clinical outcome of Leishmania infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
030231 tropical medicine
Leishmania guyanensis
Population
Leishmaniasis, Cutaneous
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Interferon-gamma
Mice
03 medical and health sciences
0302 clinical medicine
Cutaneous leishmaniasis
Genotype
medicine
Animals
Humans
Interferon gamma
education
education.field_of_study
biology
business.industry
Haplotype
medicine.disease
Leishmania
biology.organism_classification
030104 developmental biology
Infectious Diseases
Haplotypes
Immunology
business
medicine.drug
Subjects
Details
- ISSN :
- 15376591 and 10584838
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Clinical Infectious Diseases
- Accession number :
- edsair.doi.dedup.....485bab15d1c0250e20a760229e2cd127