A Study On The Association Between DNA Polymorphisms Of HBS1L-MYB And HBG2 Genes With Elevated Level Of Fetal Hemoglobin

Objectives To investigate the molecular mechanics that influence elevated level of fetal hemoglobin(Hb F)in Yunnan population.In the present study,polymorphisms of rs4895440 and rs9376090 of HBS1L-MYB gene locus,rs7482144 of HBG2 gene locus,were analyzed association with the elevated level of Hb F.Methods To screening the reased Hb F individuals by hemoglobin electrophoresis and to detect ?-thalassemia gene mutation by PCR-probe method.Control group according the ratio 1:3 to collected the matching national and age from the unrelated individuals.Single nucleotide polymorphisms(SNP)of HBS1L-MYB gene locus rs4895440,rs9376090 and HBG2 gene locus rs7482144 was analyzed by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP);The HBS1L-MYB gene locus rs4895440,rs9376090 and HBG2 gene locus rs7482144 were analyzed by Hardy-Weinberg Genetic balance test,and compared SNP genotype and allele of Hb F level individuals with normal control by SPSS 19.0 to analyzed the association between SNPs and Hb F level.The individuals not only have a high Hb F level but also have a ?-thalassemia that compared the SNP genotype and allele distribution with the normal control and non-p-thalassemia individuals with a high Hb F level.Results A total of 116 specimens that have a high Hb F level from 25862 cases that run hemoglobin electrophoresis,remove 24 samples that less than a year old,92 samples with a high Hb F level were screened in our study,and 56 ?-thalassemia samples that have gene mutation had been detected from the 92 samples,and there have nine kinds of mutant genotype,were CD17(A>T)/?N,CD41-42(-CTTT)/?N,?E(GAG>AAG)/pN,IVS-?-654(C>T)/pN,CD27-28(+C)/?N,IVS-I-5(G>C)/?N,?E(GAG>AAG)/CD41-42(-CTTT),CD41-42(-CTTT)/CD41-42(-CTTT),?E(GAG>AAG)/?E(GAG>AAG).The 92 samples of high Hb F compared with 264 normal samples,we found the high Hb F level were associated with Specific haplotype of HBS1L-MYB gene locus rs4895440,rs9376090 and HBG2 gene locus rs7482144.The high Hb F level populations compared with normal populations,the rs4895440(A/T)locus homozygous mutant genotype TT was high,the respectively scale values were 40.22%and 6.44%;the heterozygosis mutant CT and homozygous mutant CC locate in rs9376090(C/T)of high Hb F level populations was obviously higher than normal populations,the respectively scale values were 50.00%and 35.23%,26.09%and 5.68%;at the same time the heterozygosis mutant GA locate in rs7482144(G/A)locus was also obviously higher,the respectively scale values were 54.35%and 28.79%.Conclusion The elevated Hb F level significantly associates with polymorphisms of HBS1L-MYB gene locus rs4895440,rs9376090 and HBG2 gene locus rs7482144.A further study of the mechanisms that up regulated Hb F level in Yunnan populations,will provides a clue for gene therapy and prevention of ?-thalassemia,which has a important clinical significance.