Study On The Relationship Between Single Nucleotide Polymorphisms Of MDM4 And Acute Myeloid Leukemia

Objective:1.To study the distribution of twelve SNPs alleles and genotypes of MDM4 gene.2.To investigate the correlation between single nucleotide polymorphisms(SNP)of MDM4 gene and acute myeloid leukemia(AML).3.The relationship between the haplotype of the MDM4 gene and AML.Methods:1.The relationship between the distribution of twelve SNPs genotypes of MDM4 gene and the susceptibility of acute myeloid leukemia.Bone marrow or peripheral blood samples were collected from 192 cases of de novo AML patients and peripheral blood samples were collected from 192 healthy controls,then the whole genome DNA were extracted.The corresponding primers of twelve polymorphic loci of MDM4 were designed.The twelve SNP loci were genotyped by means of High Resolution Melting curve(HRM).To confirm the HRM results,random selecting samples of each genotype were sequenced in Sangon.Finally,different genotype distribution between cases and healthy controls were compared..2.MDM4 gene expression levelTotal DNA of bone marrow or peripheral blood samples from twenty de novo AML patients and ten controls were extracted,the expression levels of MDM4 were detected by PCR and Real Time RT-PCR.The expression levels between cases and controls were compared and analyzed..3.Haplotype of MDM4 in AML patientsThe genotypes of ten SNPs in 192 AML patients and 192 healthy controls were analyzed using Haploview software,the correlation between the haplotype of MDM4 gene and AML were analyzed,and the haplotype and linkage disequilibrium were counted..Results:1.rs10900597-G and rs2290854-T alleles were higher in AML patients than in controls,the proportion of rs2290854-TT genotype was significantly higher in AML cases than in controls(P < 0.05).2.There were no differences in MDM4 expression in different genotypes.3.Haplotype-based association analysis revealed that the distribution of GCTTGGCGGA was significantly higher in AML patients than controls(P < 0.05);while ACTTGGTGGA was lower in AML patients than controls(P < 0.05).Conclusion:1.The proportion of rs2290854-TT genotype was significantly higher in AML cases than in controls,the rs2290854-TT of MDM4 might play an important role in the occurrence of AML and may be a genetic marker for AML susceptibility.2.The MDM4 gene haplotype GCTTGGCGGA was positively correlated with AML;while AAAAAAGGAG was negatively correlated with AML.