Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00342823
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-06-19
Brief Title:
Immunogenetics of Visceral Leishmaniasis
Sponsor:
National Human Genome Research Institute NHGRI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Immunogenetics of Visceral Leishmaniasis
Status:
COMPLETED
Status Verified Date:
2010-06-30
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Visceral leishmaniasis is a potentially fatal disease caused in South America by the protozoan Leishmania chagasi In neighborhoods with high exposure rates the outcome of human infection with L chagasi ranges from asymptomatic to a disseminated wasting disease called visceral leishmaniasis VL Several studies document familial clustering of VL in populations at risk Segregation analyses favor a genetic over an environmental model for susceptibility to L chagasi infection A peri-urban outbreak of VL near the Universidade Federal do Rio Grande do Norte UFRN in Natal northeast Brazil has allowed us to identify endemic neighborhoods with ongoing transmission of L chagasi infection Natal is ideal for this study because endemic neighborhoods are easily accessible people are motivated to cooperate with measures to control VL and other forms of leishmaniasis are not transmitted in the region Dr Jeronimo of the UFRN and Dr Mary Wilson at University of Iowa have collected clinical data and DNA from 400 VL families living in these endemic neighborhoods We have created an unprecedented cohort through which we can identify four distinct phenotypic responses after L chagasi exposure We documented familial clustering of L chagasi infection and results of both correlation and segregation analyses are consistent with the hypothesis that genetic factors predispose in part to the diverse clinical outcomes after infection Polymorphism in the TNF locus is associated with developing symptomatic as opposed to asymptomatic disease after infection We recently completed a genome-wide scan of the quantitative immune response DTH and identified potential linkage regions on chromosomes 2 13 15 and 19 We have also identified a small linkage peak on chromosome 9 for VL In our ongoing study we will next perform fine mapping of these regions using dense SNPs to identify genes that may determine susceptibility to L chagasi infection Additionally we will also analyze candidate genes for associationlinkage with susceptibility to or protection from L chagasi disease We recently identified an association on chromosome 5 with the DTH immune response among two linkage disequilibrium blocks spanning multiple immune related genes
Detailed Description:
Visceral leishmaniasis is a potentially fatal disease caused in South America by the protozoan Leishmania chagasi In neighborhoods with high exposure rates the outcome of human infection with L chagasi ranges from asymptomatic to a disseminated wasting disease called visceral leishmaniasis VL Several studies document familial clustering of VL in populations at risk Segregation analyses favor a genetic over an environmental model for susceptibility to L chagasi infection A peri-urban outbreak of VL near the Universidade Federal do Rio Grande do Norte UFRN in Natal northeast Brazil has allowed us to identify endemic neighborhoods with ongoing transmission of L chagasi infection Natal is ideal for this study because endemic neighborhoods are easily accessible people are motivated to cooperate with measures to control VL and other forms of leishmaniasis are not transmitted in the region Dr Jeronimo of the UFRN and Dr Mary Wilson at University of Iowa have collected clinical data and DNA from 400 VL families living in these endemic neighborhoods We have created an unprecedented cohort through which we can identify four distinct phenotypic responses after L chagasi exposure We documented familial clustering of L chagasi infection and results of both correlation and segregation analyses are consistent with the hypothesis that genetic factors predispose in part to the diverse clinical outcomes after infection Polymorphism in the TNF locus is associated with developing symptomatic as opposed to asymptomatic disease after infection We recently completed a genome-wide scan of the quantitative immune response DTH and identified potential linkage regions on chromosomes 2 13 15 and 19 We have also identified a small linkage peak on chromosome 9 for VL In our ongoing study we will next perform fine mapping of these regions using dense SNPs to identify genes that may determine susceptibility to L chagasi infection Additionally we will also analyze candidate genes for associationlinkage with susceptibility to or protection from L chagasi disease We recently identified an association on chromosome 5 with the DTH immune response among two linkage disequilibrium blocks spanning multiple immune related genes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-HG-N024 | None | None | None |