SEARCHING FOR HUMAN GENETIC POLYMORPHISMS ASSOCIATED WITH CONGENITAL TRANSMISION OF CHAGAS DISEASE (CTCD)

JUIZ, NA; CAYO, M; BUA, J; LONGHI SA; SCHIJMAN AG

Mar del Plata

Congreso; X Congreso Argentino de Protozoología y Enfermedades Parasitarias; 2014

Sociedad Argentina de Protozoologia

Placental alkaline phosphatase (PLAP) has been proposed as one of the receptors used by T. cruzi for placental invasion. Its encoding gene presents functional alleles: rs2014683 (A>G, decreases transcriptional activity) and rs1048988 (G>C associated with lower enzyme activity). Another placental expressed enzymes are the metalloproteinase 2 (MMP-2) and 9 (MMP-9) which degrade and remodel specific components of the extracellular matrix, and thus play a fundamental role in placental infections. It has been reported that T. cruzi infection increases MMP-2 and MMP-9 basal expression and activity in human chorionic villi explants. Some functional polymorphisms in these gene promoters are: rs243865 and rs2285053 (C>T, display a lower promoter activity in MMP-2 gene); rs3918242 (C>T enhances MMP-9 transcriptional activity) and rs2234681 (dCA repeat in MMP-9, high repetition number is associated with high promoter activity). Our aim was to compare the frequency of the above mentioned polymorphisms in DNA samples extracted from peripheral or umbilical cord blood collected from congenitally infected (CI, N = 88) and non-infected (NCI, N=103) children born to seropositive mothers. DNA was used for sequencing, and specific High Resolution Melting Analysis (HRMA) was designed for each polymorphism. This novel strategy was performed using the Type-it HRM PCR Kit (Qiagen, USA) and PCR cycling/HRMA on the Rotor-Gene 6000? Real Time cycler. Out of the tested polymorphisms, only MMP-2 rs2285053 showed significant differences, being the T allele (p=0,032), as well as the T/T genotype (p=0,018) more represented in the CI group than in the NCI group, suggesting its association with congenital transmission. Future gene expression studies of these allelic variants in placental samples from transmitting and non-transmitting women will allow demonstrate if lower MMP-2 level of expression is associated to a higher risk of transplacental transmission.