Association Studie Between IL-15Gene Polymorphism And Childhood Acute Lymphoblastic Leukemia

Objective:Interleukin15is a growth factor of NK cell and CD8+T cell. Recently, some IL-15SNPs were found to be the risk factors of minimal residual disease in childhood acute lymphoblastic leukemia and also predisposing factors of adult acute lymphoblastic leukemia in Chinese. High resolution melted curve analysis is a high throughput, accurate and cheap genotyped technology, in which the unlabeled probe method is especially suitable for known SNPs genotyping. We established the HRM-unlabeled probe method for genotyping4SNPs of IL-15(rs17007695, rs35964658, rs10519613, rs17015014) and discussed the relations with acute lymphoblastic leukemia susceptibility in Chinese children and if there was any association between IL-15gene SNPs and risk factor of poor outcome in childhood ALLMethods:173cases of ALL children and222cases of healthy control were include in this study. High resolution curve-the unlabeled probe method was using to genotype rs35964658, rs17007695, rs10519613and rs17015014of IL-15gene. SHEsis online software and SPSS17.0statistical software was used to analysis genotype distribution difference and oddi ratio between each group.Results:The genotype results of unlabeled probes were consistent with gene sequencing. On the other hand, small amplification method without temperature calibration could not distinguish wild homozygous from mutant homozygous in our research.Not difference was found in alleles and genotype distribution of rsl7007695, rs35964658, rs10519613and rs17015014between cases and control before stratification analysis. After stratifying into different groups according to age, gender and immunophenotype, we found rs17015014-CC was associated with the risk for childhood B-ALL, especially in girls. In the haplotype analysis, these four SNPs constitute five main haplotypes (minimum frequency>3%):CATG, AGCC, CATC, AGCG and CACC. Wherein, CACC had a higher frequency in case than in control (0.048vs.0.015, P=0.0057, OR3.392,95%CI:1.3578.480).Rs10519613-CC had a higher frequency in D15-M3group than in D15-M1+M2group (66.7%and28.1%, P=0.021). The haplotype CATG increased the risk of M3in bone marrow at day15(OR2.416,95%CI1.049-5.774, P=0.034). Haplotype AGTG had a low frequency in intermediate risk group and high risk group than in standard risk group.Conclusion:The high resolution melted curve analysis-unlabeled probe was a cheap, convenient, fast and accurate genotyped technology.No relationship was found for the genotypes of rs17007695, rs35964658, rs10519613with childhood ALL susceptibility. Rs17015014-CC was associated with the risk for developing childhood B-ALL, especially in girls. Haplotype CACC is associated with the higher risk of the ALL susceptibility in Chinese children.ALL children who carried rs10519613-CC genotype or CATG haplotype may in a high risk in reach M3(blasts cells>25%) in bone marrow at day15of induction treatment. Patients with AGTG type showed a low possibility in ALL-IR/HR group.