Thiopurine pharmacogenomics: association of SNPs with clinical response and functional validation of candidate genes.

ABSTRACT:

Aim

We investigated candidate genes associated with thiopurine metabolism and clinical response in childhood acute lymphoblastic leukemia.

Materials & methods

We performed genome-wide SNP association studies of 6-thioguanine and 6-mercaptopurine cytotoxicity using lymphoblastoid cell lines. We then genotyped the top SNPs associated with lymphoblastoid cell line cytotoxicity, together with tagSNPs for genes in the 'thiopurine pathway' (686 total SNPs), in DNA from 589 Caucasian UK ALL97 patients. Functional validation studies were performed by siRNA knockdown in cancer cell lines.

Results

SNPs in the thiopurine pathway genes ABCC4, ABCC5, IMPDH1, ITPA, SLC28A3 and XDH, and SNPs located within or near ATP6AP2, FRMD4B, GNG2, KCNMA1 and NME1, were associated with clinical

SUBMITTER: Matimba A 

PROVIDER: S-EPMC4027966 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature