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Blood, Vol. 114, Issue 7, 1383-1386, August 13, 2009
Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia
Blood Ansari et al.
114: 1383
Supplemental materials for: Ansari et al
Files in this Data Supplement:
- Table S1. Identity of polymorphisms and details of PCR and ASO hybridization (PDF, 27.6 KB)
- Table S2. Cox regression models combining MRP variants with other prognostic factors or at risk genotypes (PDF, 64.7 KB)
- Figure S1. MRP gene polymorphisms and promoter haplotypes (JPG, 41.3 KB)
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(A) Haploview LD display for eight selected MRP polymorphisms. Eight MRP4 polymorphisms located in regulatory (2kb preceding transcription initiation site) and coding regions of MRP4 gene. Frequency of minor alleles in control population is given below position of each SNP. All control individuals were Caucasians (French-Canadians composed of 31 females and 18 males with the mean age of 42 years). Minor allele is underlined in the base substation, which indicates the change from ancestral to derived allele. SNPs selected for the analysis in ALL patients are encircled. The tag SNPs were selected based on linkage disequilibrium (LD) information (r2 ≥ 0.94) using Haploview software* Pair-wise r2 values are indicated. Genotype frequencies were in agreement with Hardy-Weinberg equilibrium. (B) Haplotypes arbitrarily named from *A to *D derived from 4 promoter polymorphisms. Among four polymorphisms in regulatory region two tag SNPs were identified which defined four promoter haplotypes, arbitrarily named *A, *B *C and *D, three haplotypes (*A to*C) were common (≥6%). The haplotype frequency in controls is given next to the haplotypes.
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–265.
- Figure S2. EFS curves according to combined DHFR, TS and MRP4 event-predisposing genotypes (JPG, 45.5 KB)
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The EFS curves for patients having different number of at risk genotypes are given in shades of gray. None (0) is absence of DHFR, TS and MRP4 at risk genotypes, one (1) is presence of either DFHR or TS at risk genotype, two (2) is presence of both DHFR and TS, given along with MRP4 alone (MRP4) or MRP4 combined with other genotype at risk (MRP4+1). The number of patients with all three at risk genotypes were too low (4 patients) and they were excluded from the analysis. No departure from multiplicative effect was noted for combined at risk genotype. Event-predisposing genotype for DHFR was presence of at least one copy of haplotype *1, for TS, it was homozygosity for 3R allele and for MRP4, AC934 genotype.
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