Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis
نویسندگان
چکیده
BACKGROUND Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute. METHODS AND FINDINGS In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting. CONCLUSIONS These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite.
منابع مشابه
Host genetic and epigenetic factors in toxoplasmosis.
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 o...
متن کاملGenetic Characterization of Toxoplasma gondii Isolated from Chicken Meats in Tunisia
Background: Toxoplasmosis is one of the most important food-borne diseases distributed worldwide. In order to determinate the involvement of poultry meat in clinical toxoplasmosis, this study aimed to genetic characterization of Toxoplasma gondii in tissue samples of serologically positive chickens of Tunisia using Polymerase Chain Reaction (PCR). Methods: Trail of isolation of local T. gondii...
متن کاملHigh burden of congenital toxoplasmosis in the United States: the strain hypothesis?
Rima McLeod, the leading author of an article published in this issue of Clinical Infectious Diseases [1], has accumulated a unique and remarkable database on congenital toxoplasmosis in the United States through the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS), which began in 1981 and continues to date. In a recent study [2], she and colleagues at the reference ...
متن کاملinvestigation of the prevalence of toxoplasma antibodies in women during marriage consultation in Kerman city
based on serological,toxoplasmosis infection is a widespread disease.with regard to this fact and because of the occurence of congenital toxoplasmosis infections due to asymptomatic infections in pregnant women,determination of the rate of toxoplasma antibodise(IgG,IgM) before pregnancy and finding the involved factors in increasing toxoplasmosis prevalence seems to be necessary.in this cross s...
متن کاملDetermination of the frequency and response to treatment of ocular lesions in children with various types of intrauterine infections (cytomegalovirus and toxoplasmosis): brief report
Background: Intrauterine infections (TORCH) lead to the involvement of various organs of the body of the fetus, including the eye. The aim of this study was to determine the frequency and clinical response of eye lesions to specific drugs, in infants with confirmed TORCH induced ocular lesions. Methods: This historical cohort study from 2011 to 2017, had done in Pediatrics and Ophthalmology De...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- PLoS ONE
دوره 3 شماره
صفحات -
تاریخ انتشار 2008