CYP3A4*18 and CYP3A5*3 Polymorphisms in Modulating Susceptibility Risk in Malaysian Chronic Myeloid Leukaemia Patients
10.21315/aos2020.15.1.411
- Author:
Najlaa Maddin
1
,
2
,
3
Author Information
1. Azlan Husin
2. Baba Abdul Aziz
3. Ravindran Ankathil
- Collective Name:Azlan Husin; Baba Abdul Aziz; Ravindran Ankathil
- Publication Type:Journal Article
- Keywords:
CYP3A4*18;
CYP3A5*3;
polymorphisms;
chronic myeloid leukaemia;
susceptibility risk
- From:Archives of Orofacial Sciences
2020;15(1):23-33
- CountryMalaysia
- Language:English
-
Abstract:
CYP3A4 and CYP3A5 are metabolizing enzymes abundantly expressed in liver and involved in
the metabolism of xenobiotics as well as clinically used drugs. Genetic polymorphisms in CYP3A4
and CYP3A5 may alter the metabolic ability of individuals. Thus, CYP3A4 and CYP3A5 might play
an important role in the aetiology of chronic myeloid leukaemia (CML) and as modulators of cancer
therapy response. In this study, the impact of two single nucleotide polymorphisms (SNPs) CYP3A4*18
(878T>C) and CYP3A5*3 (6986A>G) on CML susceptibility risk was investigated. This case-control
study involved a total of 520 study subjects comprising 270 CML patients and 250 normal healthy
controls. Genotyping of CYP3A4*18 and CYP3A5*3 was performed by polymerase chain reaction –
restriction fragment length polymorphism (PCR-RFLP) technique. The association between allelic
variants and CML susceptibility risk was assessed by logistic regression analysis, deriving odds ratio
(OR) with 95% confident intervals. The results showed that heterozygous (*1/*1*8) genotype of
CYP3A4*18 was significantly associated with CML susceptibility risk (OR 3.387; 95% CI: 1.433–8.007,
p = 0.005). No homozygous variant (*18/*18) genotype was detected in this study. On the contrary,
homozygous variant (*3/*3) and heterozygous (*1/*3) genotypes of CYP3A5*3 were associated with
significantly lower risk for CML susceptibility (OR 0.140; 95% CI: 0.079–0.246’ p < 0.001 and OR
0.310; 95% CI: 0.180–0.535, p < 0.001, respectively). The results prompt us to conclude that genetic
variation in CYP3A4*18 may contribute to a higher risk whereas CYP3A5*3 polymorphism confers a
lower susceptibility risk in Malaysian CML patients.
- Full text:1.2020my185.pdf
