The functional polymorphism in the ABCB1 3435C>T (rs1045642) influences the risk of chronic myeloid leukemia

ANADÓN MR; FERRI C; LARRIPA IB; WEICH N; BENGIÓ R; FUNDIA AF; FONTECHA MB; MOIRAGHI B

CABA

Simposio; Frontiers in Bioscience 3; 2018

Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA, CONICET ? Partner Institute of the Max Planck Society)

ABCB1 gene encodes the P-glycoprotein (P-gp) which is involved in detoxification of toxins and drugs through the active transport outside the cells. Although P-gp was initially associated with multidrug resistance, it is increasingly considered because its significance in cancer development. ABCB1 polymorphisms may either change its protein expression or alter its function and have also been associated with cancer risk, but their role in chronic myeloid leukemia (CML) susceptibility remains unclear. The present study aimed to investigate the relationship between CML risk and the functional common variant ABCB1 3435C>T (rs1045642). Genotyping was performed by an allele specific PCR method followed by electrophoresis on 4% 3:1 NuSieve/agarose gels in 167 treated patients and 173 sex- and age matched healthy individuals. Hardy-Weinberg Equilibrium (HWE) was tested by Chi-square test. Standard genetic models (additive, recessive and dominant) for disease penetrance were evaluated by the SNPstat online software. Allele frequencies observed in controls were in HWE (p=0.54). Genotype frequencies from patients were as follow: CC (0.28), CT (0.41) and TT (0.31), while those from controls were 0.29, 0.52 and 0.19, respectively. The frequency of the homozygous variant genotype 3435 TT was higher in patients (31%) than in controls (19%), while the frequency of the heterozygous 3435CT was inversely higher in controls than in patients (52% vs. 41%). Homozygous (CC vs. TT) and heterozygous (CC vs. CT) comparisons showed no significant differences between patients and controls. Logistic regression analysis adjusted for age and gender considering the recessive model, revealed that subjects carrying 3435TT genotype were associated with a twofold risk to develop CML when compared to the combined genotypes 3435CC-CT carriers (p= 0.015; OR: 2.24; CI: 1.16-4.33). These findings demonstrate that the ABCB1 3435C>T gene polymorphism might be a genetic risk factor and a potential biomarker for CML development.