Association of Cytochrome P450 2 E1 (C1053T) and NADPH Quinone Oxide Reducatase 1(C609T) (C 465T) Genes Polymorphism with Acute Lymphoblastic Leukemia in Sudanese Patients

Abstract

This was retrospective analytical case control study conducted at SUST in Khartoum State during the period of May 2016-January 2019, aimed to investigate the association of cytochrome P450 2 E1 (C1053T) and NAD(P)H: quinone oxidoreducatase 1(C609T) (C 465T) genes polymorphism and development of acute lymphoblastic leukemia in Sudanese patients . A total of 204 subjects were involved in this study, 102 ALL patients and 102 healthy volunteers as controls (1:1) matched age and sex. Five ml venous blood samples were collected from each subject in EDTA blood container, 2.5 ml of blood sample was analyzed by automated hematology analyzer for measurement of complete blood counts for case group and control group and flow cytometer used to identify ALL type and subtypes among patients group, the remaining 2.5 ml used for Polymerase chain – Restriction Fragment Length Polymorphism (PCR-RFLP) technique to detect genetic polymorphisms for CYP2E1(C1053T), NQO1 (C609T) and NQO1 (C465T). Data were analyzed by statistical package for social science (SPSS) computer program version 25. This study included 69(67.6%) males and 33(32.4%) females with male to female ratio 2.1:1. Age ranged from1-85 years with mean age (17.6±17.68) in both groups. Based on flowcytometery results B cell type account 82(80.4%), while T-ALL account 20 (19.6%). Complete blood count for B and T- ALL types in case group as follow: Mean TWBCs was (43.6±67.29 X109/L) and (201.78 ±261.26 X109/L), mean RBCs was (2.90±0.86X10¹²/ L), and (3.158±1017X109/L), mean platelets was (53.10± 53.26X109), and (74.70± 91.633X 109/L), mean hemoglobin (Hb) level was (8.39±2.43 g/dl), and (9.70± 2.76 g /dl) and mean blast% was (68.02±19.91) and (71.25±22.759) respectively, this study showed highly statistical significant association of mean total white blood count (P= 0.000) and mean of hemoglobin concentration (P=0.038) among T-ALL cases, while other parameters as RBCs , PLTs and Blast % were statistically insignificant with ALL subtypes (P=0.287.0.168 and 0.529) respectively. Complete blood count results among study group showed mean TWBCs in ALL patients was (74.65±143.01X109/L) while in control group was (8.89±4.01 X109/L), mean RBCs (2.95±0.93X10¹²/ L) in cases and (4.58± 0.776X10¹²/L) in control group, platelets mean (57.34±62.68X10³/L) and (333.41±109.1X109/L) respectively in cases and control. Mean hemoglobin (Hb) level was (8.65±2.54 g/dl) for cases, (12.42± 2.05g /dl) for control, this difference was highly significant (P= 0.000). CYP2E1 genotypes for wild type (CC) 95(93.1%), heterozygous type (CT) 7(6.9%), while homozygous mutant (TT) not detected 0(0%) among case group, while for control group were as follows: CC 98(96.1%), CT 4(3.9%) and for TT was not detected (0%). The hererozygosity was higher in patients when compared with controls (6.9% and 3.9%, respectively), Odd ratio was 1.805 (95% CI: 0.5117-6.369, P=0.3524); however, this difference was statistically insignificant and also for alleles was insignificantly associated with risk of ALL (OR=1.776, 95% CI: 0.5119-6.167, P= 0.3592). NQO1 (C609 T) genotypes frequency for CC 76(74.5%), CT 18(17.7%) and 8(7.8%) for TT among cases, while for control group represented as CC 89(87.2%), CT 7(6.9%) and TT 6(5.9%). The hererozygosity was higher in patients compared with controls (17.7% and 6.9%) respectively, the odds ratio was 3.513 (95% CI: 1.327-9.301, P=0.0081), this difference was statistically significant, while for homozygous mutant frequency was also high in case (7.8%) than control (5.9%) with odd ratio 1.338 (95%CI 0.4638-3.862, P=0.5888), this difference was insignificant. Alleles frequency was significantly associated with risk of ALL (OR=1.840, 95% CI: 1.019-3.321), P= 0.0408). Frequency of NQO1 (C465T) genotypes for CC, CT, and TT genotypes among patients with ALL were 72(70.6%), 23(22.5%) and 7(6.9%) respectively, while in control group were distributed as follows: 94(92.2%), 5(4.9%) and 3(2.9%) respectively. The hererozygosity was higher in patients compared with controls (22.5% and 4.9%, respectively); this difference was statistically highly significant, the odds ratio was 7.667 (95% CI: 2.539-23.15, P =0.0001) and for homozygous mutant was also high in case(6.9%) than control(2.9%) with odd ratio 4.667 (95%CI 0.9410-23.14, P = 0.0401), alleles frequency also significant associated with risk of ALL (OR=2.7, 95% CI: 1.427-5.107), P = 0.0017). In conclusion: This study concluded that NQO1 (C609T) and (C465T) considered as risk factors for ALL development in Sudanese population, while CYP2E1 (C1053T) polymorphism was not associated with risk of ALL.