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

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

Mar del Plata

Congreso; VI SLIMP & V LASRI,; 2015

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). Objetives: to compare the frequency of the 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. Methods: 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) and PCR/HRMA on Rotor-Gene 6000? Real Time cycler.Results: 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. Conclusions: 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. In addition, other MMP -2 SNPs (rs243866, rs243864 and rs17859821) will be studied to elucidate if there is any haplotype that confers fetal susceptibility.