Host genetic and epigenetic factors in toxoplasmosis
Mem. Inst. Oswaldo Cruz
;
104(2): 162-169, Mar. 2009. tab, ilus
Article
in English
| LILACS
| ID: lil-533502
ABSTRACT
Analysing human genetic variation provides a powerful tool in understanding risk factors for disease. Toxoplasma gondii acquired by the mother can be transmitted to the fetus. Infants with the most severe clinical signs in brain and eye are those infected early in pregnancy when fetal immunity is least well developed. Genetic analysis could provide unique insight into events in utero that are otherwise difficult to determine. We tested the hypothesis that propensity for T. gondii to cause eye disease is associated with genes previously implicated in congenital or juvenile onset ocular disease. Using mother-child pairs from Europe (EMSCOT) and child/parent trios from North America (NCCCTS), we demonstrated that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4 previously associated with juvenile onset retinal dystrophies including Stargardt's disease. Polymorphisms at COL2A1 encoding type II collagen, previously associated with Stickler syndrome, associated only with ocular disease in congenital toxoplasmosis. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting, which provided an explanation for the patterns of inheritance observed. These genetic and epigenetic risk factors provide unique insight into molecular pathways in the pathogenesis of disease.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Toxoplasmosis, Congenital
/
Toxoplasmosis, Ocular
/
Toxoplasmosis, Cerebral
/
ATP-Binding Cassette Transporters
/
Collagen Type II
Type of study:
Risk factors
Limits:
Female
/
Humans
/
Infant, Newborn
/
Pregnancy
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2009
Type:
Article
Affiliation country:
Australia
/
Denmark
/
United States
/
United kingdom
Institution/Affiliation country:
Aarhus University Hospital/DK
/
Cambridge Institute for Medical Research/AU
/
Telethon Institute for Child Health Research/AU
/
University College London/GB
/
University of Chicago/US
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