HBG基因启动子区rs368698783、rs7482144位点多态性与HbF表达相关  

Polymorphisms at rs368698783 and rs7482144 loci in the promoter region of the HBG gene are associated with HbF expression

作　　者：邓玲 龙岚 杨阳 靳婵婵 李苏云[2] 丰娜 贺静[2] DENG Ling;LONG Lan;YANG Yang;JIN Chanchan;LI Suyun;FENG Na;HE Jing(Medical School&Affiliated Hospital,Kunming University of Science and Technology,Kunming 650032;Department of Medical Genetics,the First People's Hospital of Yunnan Province,Kunming 650032,China)

机构地区：[1]昆明理工大学医学院&附属医院,云南昆明650032 [2]云南省第一人民医院医学遗传科,云南昆明650032

出　　处：《基础医学与临床》2023年第2期211-218,共8页Basic and Clinical Medicine

基　　金：国家自然科学基金(81860030);云南省技术创新人才培养项目(2019HB071);云南省临床医学中心开放项目(2019LCZXKF-XY04)。

摘　　要：目的探讨云南β-地中海贫血(地贫)患者rs368698783和rs7482144多态性位点与胎儿血红蛋白(HbF)表达的相关性。方法收集β-地贫样本51例,HbE纯合样本40例,HbF>5%(β^(N)/β^(N))样本113例,HbF>5%(β^(M)/β^(N))样本113例,对照组262例,共579例样本。采用Sanger测序法对rs368698783及rs7482144位点进行检测,比较各组血液学参数、突变基因检出率和最小等位基因频率(MAF),分析该多态性位点与HbF水平之间的关系。结果非输血依赖性β-地贫患者的rs368698783与rs7482144位点的突变基因检出率和MAF显著高于对照组(P<0.05)。HbE纯合样本的rs368698783与rs7482144位点的突变基因检出率和MAF显著高于对照组(P<0.001)。HbF>5%(β^(N)/β^(N))、HbF>5%(β^(M)/β^(N))样本rs368698783与rs7482144位点突变基因检出率和MAF显著高于对照组(P<0.001)。结论rs368698783与rs7482144位点的多态性与HbF水平升高有关,并且与HbE突变存在相关性,rs368698783的A等位基因与rs7482144位点的T等位基因可以减轻β-地贫的贫血程度,缓解β-地贫的临床症状。Objective To investigate the correlation between rs368698783 and rs7482144 locus and fetal hemoglobin(HbF)expression inβ-thalassemia patients of Yunan province.Methods A total of 579 samples were collected,including 51 samples ofβ-thalassaemia,40 samples with HbE,113 samples of HbF>5%(β^(N)/β^(N)),113 samples of HbF>5%(β^(M)/β^(N))and 262 samples from controls.Sanger sequencing was used to determine the genotypes of rs368698783 and rs7482144.The relationship between rs368698783 and HbF levels was analysed by comparing haematological parameters,mutant gene detection rates and MAF.Results The detection rate and MAF of mutated genes at the rs368698783 and rs7482144 loci were significantly higher in non-transfusion-dependentβ-thalassaemia patients than that in controls(P<0.05).The detection rate and MAF of mutated genes at the rs368698783 and rs7482144 loci were significantly higher in HbE pure samples than that in controls(P<0.001).The detection rates of mutated genes and MAF at rs368698783 and rs7482144 loci were significantly higher in HbF>5%(β^(N)/β^(N))and HbF>5%(β^(M)/β^(N))samples than in the control group(P<0.001).Conclusions The rs368698783 and rs7482144 mutation is associated with elevated HbF level and with HbE mutations.The A allele and T allele can reduce the degree of anaemia and alleviate the clinical symptoms ofβ-thalassemia.

关 键 词：Β-地中海贫血 胎儿血红蛋白 rs368698783 rs7482144 

分 类 号：R556[医药卫生—血液循环系统疾病]