AUTHOR=Gándara-Mireles Jesús Alonso , Lares-Asseff Ismael , Reyes Espinoza Elio Aarón , Blanco Javier G. , Chairez Hernández Isaias , Córdova Hurtado Lourdes Patricia , Loera Castañeda Verónica , Patrón Romero Leslie , Venzor Sánchez Cristina , Payan Gándara Hugo , Arechiga Gurrola Dinora , Almanza Reyes Horacio 

TITLE=Genotype Analysis of ABCC1, NCF4 and CBR3 Polymorphism and the Association With Childhood Acute Lymphoblastic Leukemia in Mexican Childhood Population

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.616630

DOI=10.3389/fphar.2020.616630

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary.</p><p><bold>Objective:</bold> The purpose of this study is to determine the association of the genetic polymorphisms <italic>ABCC1</italic> rs3743527, <italic>NCF4</italic> rs1883112 and <italic>CBR3</italic> rs1056892 with ALL.</p><p><bold>Methods:</bold> DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne<sup>®</sup> thermal cycler (Applied Biosystems, United States).</p><p><bold>Results:</bold> The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880–7.9383 and <italic>p</italic> = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and <italic>p</italic> = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and <italic>p</italic> = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and <italic>p</italic> = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and <italic>p</italic> = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and <italic>p</italic> = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and <italic>p</italic> = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and <italic>p</italic> = 0.05).</p><p><bold>Conclusion:</bold> There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.</p>