Association of Multidrug Resistance Gene-1 (MDR1 C1236T) Polymorphism with the Risk of Acute Myeloid Leukemia in a Moroccan Population.

Oum Kaltoum Ait Boujmia,Mouna Lamchahab,Hind Dehbi,Asma Quessar,Sellama Nadifi

doi:10.31557/apjcp.2020.21.7.1899

Abstract

The human multidrug resistance MDR1 gene plays a crucial role in the absorption, transport, metabolism and elimination of harmful compounds. An impaired metabolism of these compounds related to genetic polymorphism may cause cancer such as acute myeloid leukemia AML. Objective:The present study investigated the relationship between C1236T polymorphism and the risk of AML development in a sample of Moroccan population. Methods:The present case-control study included 131 AML patients and 136 healthy controls. The MDR1 C1236T polymorphism was identified by PCR-RFLP method. Meta-analysis was performed to discuss our results. Statistical analyses were performed using SPSS, MetaGenyo and MedCalc. Results:A positive association was found between the 1236TT mutant genotype and the risk of AML (OR 2.39; 95% CI 1.02-5.57, p= 0.04) compared to the wild type 1236CC. In addition, the recessive model revealed that carriers of 1236TT mutant genotype were more exposed to develop AML when compared to the combined 1236CC/CT genotype (OR: 2.27, CI: 1.01–5.05, p=0.04). The clinical parameters of AML showed no significant association. Meta-analysis demonstrated no statistically significant association between this polymorphism and AML susceptibility. Conclusion:Our study suggests that the MDR1C1236T polymorphism appears to be associated with the risk of AML. Further studies, including a large sample size, are needed to confirm these findings.

Highlights

Acute myeloid leukemia (AML) is the most deadly type of leukemia (GB, 2016)
The recessive model revealed that carriers of 1236TT mutant genotype were more exposed to develop AML when compared to the combined 1236CC/CT genotype (OR: 2.27, confidence intervals (CI): 1.01–5.05, p=0.04)
A random-effects model was used to estimate common odds ratio (OR) if heterogeneity was detected; I2> 50% indicated heterogeneity between studies. In this case-control study, we examined the impact of C1236T MDR1 gene polymorphism on the risk of developing AML in 131 patients with AML and 136 healthy controls

Summary

Introduction

Acute myeloid leukemia (AML) is the most deadly type of leukemia (GB, 2016). As other types of cancer, the etiology of AML remains unknown. Many risk factors were incriminated such as exposition to pesticides, radiotherapy, chemotherapy, benzene and radiation (Zeeb and Blettne, 1998; Smith et al, 2011). Many genes have been reported to be associated with higher risk of AML. MDR1 or ABCB1 gene is expressed in organs implicated in xenobiotics metabolism and excretion (the gastrointestinal system, kidney and liver). The alteration of MDR1 activity related to interindividual genetics background may lead to the development of cancers (Laura et al, 2011; Urayama et al, 2007; Ambudkay et al, 1999; Schimkel, 1997; Hattori et al, 2007)

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