| ?-thalassemia Intermedia(?-TI)has a large phenotypic heterogeneity,and its modifiers mainly include ?-globin gene mutation types,modify genes that affect the expression of y-globin gene,and a-globin gene mutations and so on.Among them,the related researches on the modify genes affecting the expression of y-globin genotype focus on some cis-expression and trans-acting factors that can regulate Hb F levels.In recent years,studies have found that HBBP1(rs2071348),HBG2(rs7482144),and HBS1L-MYB(rs9399137)single nucleotide polymorphisms are associated with Hb F levels,but the relationship are different between these three sites and Hb F in different regions and populations.The relevance of the F level is not thesame,showing a clear difference in geography and population distribution.At present,there is a lack of systematic research data for the relationship between the genetic modification factor of the ?-thalassaemia Intermedia in Chinese population.The ?-globin gene mutation type is also one of the factors affecting the phenotypic heterogeneity of ?-TI.In addition to the severity of ?-thalassemia mutations,some abnormal hemoglobin mutations are also compounded with ?-thalassemia mutations.?-TI,such as HbE and Hb Rush.HbE is the most frequent type of ?-globin gene mutation in Yunnan and has a high incidence in different ethnic groups.Hb Rush is a rare mutation and 17 heterozygous carriers have been discovered in the Dehong area of Yunnan.The origin and the time of occurrence of these two mutations in the Yunnan region are still unknown.Yunnan is one of the regions with high incidence of thalassemia in China.HbE/?-thalassaemia mutations are the most common type of intermediate ?-thalassemia mutations.Especially in the southwest of Yunnan Province,Dehong Dai Jingpo ethnic group has the highest incidence of thalassemia and there are many intermediate?-thalassemia among the population.However,there are few reports on the clinical heterogeneity of the performance and genetic modification factors.Therefore,to explore the relationship between genetic polymorphisms and clinical heterogeneity in the population in this area,and to further understand the nature of ?-thalassemia modification factor is of great significance.[Objective]This study was to analyze the genetic polymorphisms of HBBP1,HBG2 and HBSlL-MYB in Dehong,Yunnan,in four different groups of HbE patients,?-thalassemia patients,and HbE/?-thalassaemia patients and the normal population.The distribution characteristics of the above-mentioned genetic modification site gene polymorphisms and Hb F correlation;at the same time analyze whether the distribution of Hb Rush and HbE mutations in Yunnan caused by the founder effect,and speculate that the mutation carrier may origin and recent The time when the common ancestor existed.[Methods]When we analyze the association between the genetic modification loci and Hb F level,the genotype of HBBP1(rs2071348),HBG2(rs7482144),and HBSIL-MYB(rs9399137)were detected using ARMS-PCR and PCR-RFLP in 41 cases of HbE/beta-thalassaemia,98 cases of beta-thalassemia,89 cases of HbE and 190 normal controls,and analyzed their association with Hb F;When we analyze the origin of Hb Rush mutations,capillary electrophoresis was used to detect 12 STRs in 17 Hb Rush carriers and 170 normal controls.Common haplotypes were used to analyze the possible origin of the mutation.When we analyze the origin of HbE mutations,capillary electrophoresis was used to detect 12 STRs in HbE carriers of 17 De,ang people,19 Jingpo people,12 Dai people,8 Achang people,and normal controls of 75 De'ang people,80 Jingpo people,61 Dai people,72 Achang people.Common haplotypes were used to analyze the possible origin of the mutation.Using ESTIAGE to estimate the age of common ancestors.[Results](1)The results of comparing the Hb F level and SNP allele distribution between the groups were:Hb F levels in the HbE/?-thalassam group were significantly higher than those in the normal control group,and in the HBBP1(rs2071348)The Minor Allele Frequency(MAF)of the two points of HBG2(rs7482144)was C allele(0.87)and T allele(0.64),which was significantly higher than that of the normal control group,There was no significant difference between the HBS1L-MYB(rs9399137)locus and the normal control group;the HbF level in the HbE group was higher than the normal control group,and in the HBBP1(rs2071348)and HBG2(rs7482144)two The MAFs of the sites were C(0.84)and T(0.89),which were significantly higher than the normal control group.There was no significant difference between the HBS1L-MYB(rs9399137)loci and the normal control group;The level of Hb F in the poor group was not significantly different from that in the normal control group.The MAF in the HBSIL-MYB(rs9399137)locus was C allele(0.24),which was significantly higher than that in the normal control group.The MAF of HBBP1(rs2071348)was C(0.06),which was significantly lower than that of the normal control group.The MAF of HBG2(rs7482144)was T(0.08),which was not significantly different from the normal control group.The association analysis between the SNP allele and Hb F level in the group was:the gene of the HBBPl(rs2071348)locus in the normal control group.There was a significant correlation between type and Hb F levels,and no correlation between SNP polymorphisms and Hb F levels was found in other groups.(2)11 Hb Rush carriers shared a haplotype of 203-217-108-173 at four STR loci in D11S1883,D11S4181,D11S1760,and D11S4124.The common ancestry time was 51 generations,and the 95%confidence interval was 36 to 75 generations.(3)Four Dai HbE carriers share a haplotype of 203-217-108-173 at the four STR loci mentioned above,and the frequency of the haplotype in the normal control of Dai is 0.073;7 Jingpo HbE carriers A haplotype of 203-217-108-173 was shared among the above four STR loci,the frequency of the haplotype in the normal control of the Jingpo tribe was 0.188;6 De' ang HbE carriers were in the above four STR loci A haplotype of 203-217-108-173 was shared,and the frequency of this haplotype in the normal Deang ethnic control was 0.080;Two Achang HbE carriers shared a 203-217-108 at the above four STR loci.The frequency of this haplotype in the Achang normal controls was 0.069.[Conclusion](1)HBBP1(rs2071348),HBG2(rs7482144)and HBS1L-MYB(rs9399137)are polymorphic in the population of Dehong,Yunnan;(2)HBBP1(rs2071348)and HBG2(rs7482144)polymorphisms may have a functional association with HbE mutations.(3)The two polymorphisms of HBBP1(rs2071348)and HBG2(rs7482144)may be associated with Hb F protein levels,and the clinical manifestation heterogeneity of intermediate beta-thalassemia may be due to the nature and population of ?-globin gene mutations.The combined effects of genetic modifiers.(4)Hb Rush mutat.ions in Yunnan population may have a common ancestor.Their common ancestors were about 1020 years ago.The distribution in Yunnan population is mainly due to the founder effect of mutation.(5)The HbE mutation in the Dai,Jingpo,Deang and Achang populations in Yunnan may not from a common ancestor. |
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