Association of genetic polymorphisms of the ABCG2, ABCB1, SLCO1B3 genes and the response to Imatinib in chronic myeloid leukemia patients with chronic phase

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• 作者：Devika Nair^a ; Somprakash Dhangar^a ; Chandrakala Shanmukhaiah^b ; Babu Rao Vundinti^a ; ^{vbaburao@hotmail.com}
• 关键词：Chronic myeloid leukemia ; Imatinib ; Pharmacokinetics ; BCR-ABL independent mechanisms ; Single nucleotide polymorphism ; Drug resistance
• 刊名：Meta Gene
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：11
• 期：Complete
• 页码：14-19
• 全文大小：607 K
• 卷排序：11

文摘

Inter-individual variability to Imatinib response among chronic myeloid patients has led to the hunt for mechanisms responsible for such variability. Screening of single nucleotide polymorphisms (SNPs) in transmembrane transporter genes is a common approach employed to decipher its role in influencing the pharmacokinetics of Imatinib. The focus of the current study was screening of SNP's in candidate genes, which may be involved in the transport of Imatinib (efflux or influx), thereby affecting its bioavailability. Our results revealed a statistically insignificant association between the SNP's in the ABCG2 and ABCB1 genes (rs2231142, rs2231137, rs1045642, rs2032582). However, a statistically significant association was observed between the SLCO1B3 (rs4149117) genotype and cytogenetic response. The SLCO1B3 334TT genotype was found to be associated with a higher risk of failure of cytogenetic response (OR = 13.36, 95% CI: 0.622-287.2, P = 0.04), while the patients with SLCO1B3 334GT/GG genotype showed a higher probability of achieving a complete cytogenetic response at 6 months (OR = 0.127, 95% CI: 0.016–1.008, P = 0.04). Our results therefore, suggest that SLCO1B3 334T > G genotype may be of clinical importance in the prediction of treatment outcome to Imatinib.