| Objective To study the correlativity of BCL11A genes(rs11886868,rs766432,rs4671393),HBS1L-MYB genes(rs9399137,rs4895441,rs35959442),XmnI-HBG2 gene(rs7482144)polymorphism and Fetal hemoglobin(Fetal hemoglobin,HbF)in Guangxi β-thalassemia major patients.Methods The study included 105 cases of Guangxi β-thalassemia major p atient samples and 100 cases of normal control samples.7 polymorphic loci among BCL11A gene,HBS1L-MYB genes and XmnI-HBG2 gene(BCL 11A:rs4671393,rs766432,rs11886868;HBS1L-MYB:rs35959442,rs4895441,rs9399137,XmnI-HBG2:rs7482144)were detected by Polymerase ch ain reaction-restriction fragment length polymorphism(PCR-RELP)and DNA sequencing technology.Comparing the differences in gene frequencies and genotype distribution between the case group and the normal group,a nd analyze the correlation of those 7 polymorphic loci with the HbF level.Results1.The gene mutation frequency of rs4671393 and rs766432 loci of BCL 11A gene were significantly higher in β-thalassemia major group than that in normal control group and these two groups genotype distribution show difference,.as the difference had significance of statistics(P<0.05).The cor relation analysis of rs4671393 and rs766432 loci showed that they have si gnificant association with the level of HbF(rs4671393:rs=0.772,P<0.001;rs766432:rs=0.744,P<0.001).While in β-thalassemia major group and n ormal control group can not found mutations in rs11886868 loci and it ha s no correlation with HbF(P>0.05).2.The allele frequency of rs4895441 and rs35959442 loci among HBS1 L-MYB were both significantly higher in β-thalassemia major group than that in normal control group;the difference had significance of statistics(P<0.05).The genotype distribution of rs4895441 in β-thalassemia major g roup difference with that in normal control group;the difference had signi ficance of statistics(P<0.05).The correlation analysis of rs4895441 and rs 35959442 loci showed that they have significant association with HbF lev el(rs4895441:rs=0.506,P<0.001;rs35959442:rs=0.497,P<0.001).Only 2 cases of rs9399137 loci of mutations type have found in beta-thalassemia major group,and have no correlation with HbF level(P>0.05).3.The allele genotype frequency and genotypic distribution at XmnI-H BG2 gene rs7482144 loci in β-thalassemia major group and in normal co ntrol group has no significance of statistics(P>0.05).The correlation anal ysis of rs7482144 showed that it has low correlation with HbF level(rs =0.328,P<0.001).4.In linkage disequilibrium analysis the rs4671393 site and rs766432 site of BCL11A that D’=0.702,which was highly linkage disequilibrium.Co rrelation coefficient of HbF and mutation genotype that with rs4671393 site but without rs766432 site was 0.466(P<0.05);correlation coefficient of HbF and mutation genotype that with rs766432 locus mutation but without rs4671393 was 0.378(P<0.05);correlation coefficient of HbF and muta tion genotype that both with rs4671393 loci and rs766432 sites was 0.802(P<0.05).rs9399137 locus,rs4895441 locus and rs35959442 locus of HB S1L-MYB gene were all in linkage disequilibrium.Conclusion1.The polymorphisms of rs4671393,rs766432,rs35959442,rs4895441,rs9399137,rs7482144 variants in BCL11A gene,HBS1L-MYB genes and Xmn I-HBG2 gene were exist in Guangxi region.,2.(1)The allele frequency and genotype frequency were difference at rs4671393,rs766432,rs4895441 loci in case and control groups.The allele frequency of rs35959442 loci has differences in case and control groups.(2)The mutation frequency of rs 11886868 and rs9399137 loci is low in Guangxi region.3.These mutation,such as rs4671393G→A mutation,rs766432A→C m utation,rs4895441A→G mutation,rs35959442C→G mutation,rs4782144G→A mutation,which will increase HbF level in β-alassemia major of patients in Guangxi region.4.It may be relevance between rs4671393 and rs766432 loci and it have the synergy function of HbF. |
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