AUTHOR=Zaruma-Torres Fausto , Lares-Asseff Ismael , Lima Aurea , Reyes-Espinoza Aarón , Loera-Castañeda Verónica , Sosa-Macías Martha , Galaviz-Hernández Carlos , Arias-Peláez María C. , Reyes-López Miguel A. , Quiñones Luis A. 

TITLE=Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

JOURNAL=Frontiers in Pharmacology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00238

DOI=10.3389/fphar.2016.00238

ISSN=1663-9812

ABSTRACT=<p>Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. <italic>COL18A1</italic> (rs2274808), <italic>SLC19A1</italic> (rs2838956), <italic>ABCB1</italic> (rs1045642 and rs1128503), and <italic>ABCC5</italic> (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11–5.83, <italic>p</italic> = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62–78.87, <italic>p</italic> &lt; 0.0001) of <italic>COL18A1</italic> rs2274808; in <italic>SLC19A1</italic> rs2838956 AG carriers (OR = 44.69, CI 95% 10.42–191.63, <italic>p</italic> = 0.0001); in <italic>ABCB1</italic> rs1045642 TT carriers (OR = 13.76, CI 95% 5.94–31.88, <italic>p</italic> = 0.0001); in <italic>ABCC5</italic> rs9838667 AC carriers (OR = 2.61, CI 95% 1.05–6.48, p &lt; 0.05); and in <italic>ABCC5</italic> rs3792585 CC carriers (OR = 9.99, CI 95% 3.19–31.28, <italic>p</italic> = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of <italic>ABCC5</italic> polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly <italic>COL18A1</italic> rs2274808<italic>, SLC19A1</italic> rs2838956<italic>, ABCB1</italic> rs1045642, and <italic>ABCC5</italic> rs3792585, were associated with an increased risk for ALL in Mexican children.</p>