Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

摘要: Background: Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, new ocular lesions occur at any age after birth. Not all children who acquire in utero develop these clinical signs of disease. Whilst severity disease is influenced by trimester which acquired mother, other factors including genetic predisposition contribute.Methods Findings: In 457 mother-child pairs from Europe, 149 child/parent trios North America, we show that brain congenital toxoplasmosis associate with polymorphisms ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms COL2A1 type II collagen only Both loci showed unusual inheritance patterns for allele when comparing outcomes heterozygous affected mothers. Modeling suggested either an effect mother's genotype, or parent-of-origin effects. Experimental studies both isoform-specific epigenetic modifications consistent imprinting.Conclusions: These associations between provide novel insight into molecular pathways this parasite.