福建省籍各地市人群地中海贫血的分子流行病学研究

Molecular epidemiological analysis of α- and β- thalassemia in Fujian province

目的了解福建省籍各地市人群地中海贫血（简称地贫）的基因携带率、基因突变类型及其分布特征。方法采用分层整群方法随机抽取福建省9地市籍贯体检人群的静脉血，测定红细胞参数和用高效液相色谱法分析血红蛋白，表型阳性的标本用单管多重PCR方法检测中国人常见的3种α缺失型突变和PCR-寡核苷酸探针反相斑点杂交法检测非缺失α地贫基因突变及β-地贫基因突变。未知突变采用DNA直接测序法进行分析。结果11 234人中，共检出α和β地贫504例，地贫总携带率为4.41％。其中356例样本为α地贫，-^SEA／αα236例、-α^3.7／αα67例、-α4.2／αα24例、血红蛋白H病4例（-α3.7／-^SEA3例，-α4.2／-^SEA1例）、-α3.7／-α3.7 1例、-α3.7／-α4.2 1例、非缺失型α地贫中，αα^QS／αα7例、αα^CS／αα3例、αα^WS／αα2例，最常见的为-^SEA／αα占全部基因突变的66．29％；148例为p地贫，共检出12种基因突变类型，IVS-2-654（C→T）65例、CD41-42（-TCTT）40例、CD17（A—T）12例、一28（A→G）10例、CD27→28（＋C）7例、起始密码子ATG→AGG5例、cD26（G→A）2例、CD71-72（＋A）1例、IVS-1-1（G→T）1例、CD43（G→T）1例、-29（A→G）2例、Codon36（-C）2例，其中最常见的是IVS-2-654（C→T）和CD41-42（-TCTT），占全部基因突变的70．95％，并再次在中国人群中发现了Codon36（-C）的新的突变类型。α地贫复合β地贫双重杂合子9例。结论阐明福建省籍各地市人群α和β地贫的基因突变类型和频率，在国内具有较高的地贫发生率和遗传异质性，该研究为在本地区开展遗传咨询和产前诊断提供了参考借鉴资料。

Objective To investigate the gene prevalence and spectrum of α- and β-thalassemia in Fujian province. Methods A total of 11 234 of neonatal cord blood samples were collected for a prevalence study of a and β- thalassemia. All subjects included in this study were registered in 9 cities of Fujian province. A complete blood count and high performance liquid chromatography （HPLC） were performed in all samples, with microcytosis （MCV≤79 fl and MCH≤27 pg） or HPLC positive cases further studied by DNA analysis, α- and β-thalassemia were determined by using gap-PCR and reverse dot blot （RDB） assays. Unknown positive samples were analyzed directly with DNA sequencing. Results Of all 11 234 cord blood samples, 356 were identified as from a-thalassemia gene carriers, 7 deletion genotypes were identified including 236 （-^SEA/αα） cases, 67 （-α^3.7/αα） cases, 24 （-α^4.2/αα） cases, 3 （-αα^3.7/-^SEA） cases, 1 （-α^4.2/-SEA ） cases, 1 （-α^3.7/-α^3.7 ） cases, 1 （-α^3.7/-α^4.2） cases;3 non-deletion genotypes were detected, including 7 （aaQS/aa） cases,3 （aaCS/aa） cases, 2 （aaWS/aa） cases, the most common mutation was--SEA/aa, which accounted for 66.29%,148 individuals were found to have β- hemoglobin gene mutations . 12 differentmutations were identified, namely 65 IVS-2-654 （C→T） cases, 40 CD41-42 （-TCTT）, 12 CD17 （ A→T） cases,10-28（A→G） cases,7 CD27-28（＋C） cases, 5 start eodon ATG→AGG cases, 2 CD26（G→A） cases, 1 CD71-72 （ ＋ A） eases, 1 IVS-1-1 （G→T） eases, 1 CD43 （G→T） cases, 2-29 （A→G） eases, 2 Codon 36 （-C） cases, the most common mutation was IVS-2-654 （C→T）and CD41-42 （- TCTT）, which accounted for 70.95%. A novel β-globin gene mutation CD36 （--C） allele was also detected. The carrier rate of thalassemia in Fujian population is 4.41%. In addition, 9 β-thalassemia carriers were found with α- thalassemia mutation. Conclusion The research has revealed the type of gene mutations in α- and β- talassemia in Fujian province. The β-thalassemia mutations in Fujian province are eomplex, which were also obviously heterogeneous. This will significant value for screening the incidence, provide the valuable information for genetic counseling and prenatal diagnosis.