RGD Reference Report - Association between the tumor necrosis factor locus and the clinical outcome of Leishmania chagasi infection. - Rat Genome Database

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Association between the tumor necrosis factor locus and the clinical outcome of Leishmania chagasi infection.

Authors: Karplus, TM  Jeronimo, SM  Chang, H  Helms, BK  Burns, TL  Murray, JC  Mitchell, AA  Pugh, EW  Braz, RF  Bezerra, FL  Wilson, ME 
Citation: Karplus TM, etal., Infect Immun. 2002 Dec;70(12):6919-25.
RGD ID: 8548784
Pubmed: PMID:12438370   (View Abstract at PubMed)
PMCID: PMC133071   (View Article at PubMed Central)

A periurban outbreak of visceral leishmaniasis (VL) caused by the protozoan Leishmania chagasi is ongoing outside Natal, northeast Brazil. Manifestations range from asymptomatic infection to disseminated visceral disease. Literature reports suggest that both genetic and environmental factors influence the outcome of infection. Due to the association of the tumor necrosis factor (TNF) locus with other infectious diseases, we examined whether polymorphic alleles at this locus are associated with the outcome of L. chagasi infection. Neighborhoods with ongoing transmission were identified through patients admitted to local hospitals. Altogether, 1,024 individuals from 183 families were classified with the following disease phenotypes: (i) symptomatic VL, (ii) asymptomatic infection (positive delayed-type hypersensitivity [DTH+]), or (iii) no evidence of infection (DTH-). Genotypes were determined at a microsatellite marker (MSM) upstream of the TNFB gene encoding TNF-beta and at a restriction fragment length polymorphism (RFLP) at position -307 in the promoter of the TNFA gene encoding TNF-alpha. Analyses showed that the distribution of TNFA RFLP alleles (TNF1 and TNF2) and the TNF MSM alleles (TNFa1 to TNFa15) differed between individuals with VL and those with DTH+ phenotypes. TNF1 was transmitted more frequently than expected from heterozygous parents to DTH+ offspring (P = 0.0006), and haplotypes containing TNF2 were associated with symptomatic VL (P = 0.0265, transmission disequilibrium test). Resting serum TNF-alpha levels were higher in TNF1/2 heterozygotes than in TNF1/1 homozygotes (P < 0.05). These data led us to hypothesize that an individual's genotype at the TNF locus may be associated with whether he or she develops asymptomatic or symptomatic disease after L. chagasi infection. The results preliminarily suggest that this may be the case, and follow-up with larger populations is needed for verification.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LTAHumanvisceral leishmaniasis severityIAGP DNA:polymorphismsRGD 
LtaRatvisceral leishmaniasis severityISOLTA (Homo sapiens)DNA:polymorphismsRGD 
LtaMousevisceral leishmaniasis severityISOLTA (Homo sapiens)DNA:polymorphismsRGD 
TNFHumanvisceral leishmaniasis severityIAGP DNA:polymorphismsRGD 
TnfRatvisceral leishmaniasis severityISOTNF (Homo sapiens)DNA:polymorphismsRGD 
TnfMousevisceral leishmaniasis severityISOTNF (Homo sapiens)DNA:polymorphismsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lta  (lymphotoxin alpha)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Lta  (lymphotoxin A)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
LTA  (lymphotoxin alpha)
TNF  (tumor necrosis factor)


Additional Information