广东顺德地区α-和β-地中海贫血的分子流行病学调查

The Molecular Epidemiology of αandβthalassemia in Guangdong Shunde

目的调查顺德地区α-地中海贫血和β-地中海贫血(简称"地贫")基因的携带率、基因突变类型及其频率分布。方法采集顺德地区1000例新生儿脐带血和1100例婚检育龄成人外周血分别进行α和β分子流行病学调查。α-地贫初筛的诊断标准为:Hb Bart's阳性。Hb Bart's阳性标本先进行常见的缺失型基因(—^(SEA)/、—^(3.7)/和—^(4.2)/)检测,阴性者采用膜反向杂交技术,检测6种非缺失型α-地贫突变位点(α^(CD30),△GAT;α^(CD31),G-A;α^(CD59),G-A;α^(WS),C-G;α^(QS),C-G;α^(CS),C-G)。Hb Bart's阴性标本进行2种静止型α-地贫基因(—^(3.7)/和—^(4.2)/)的检查;β-地贫初筛诊断标准为:MCV<80fL,HbA2>4.0%。β-地贫表型阳性采用多聚酶链反应-反向斑点杂交法进行17种中国人常见及少见β-地贫基因诊断。结果在1000例新生儿脐带血样本中,Hb Bart's阳性样品54例,阳性检出率为5.40%。经基因分析,共检出α-地贫基因89例,顺德地区户籍人口的α-地贫基因携带率为8.90%,基因型主要为—^(SEA)/αα、—α^(3.7)/αα2种,占总数的89.89%;在1100例婚检对象中,初筛表型阳性样品43例,经基因分析,全部携带β-地贫基因,β-地贫基因的检出率为3.91%,其中以CD41-42、IVS-Ⅱ-654、-28、CD17、βE为本地区最常见的突变位点,上述5种突变类型占所有检出突变位点的95.30%。结论顺德地区α-地贫基因携带率和基因突变类型与广东其他地区相差不大,β-地贫基因携带率比广东其他地区稍高,在预防干预中应给予重视。

Objective To investigate the α-and β-thalassemia gene＇s carrying rates,gene mutation types and frequency distribution in Shunde district. Methods 1 000 newborns＇ umbilical cord blood and 1100 antemarital adults＇ peripheral blood were acquisited for α-and β-thalassemia＇s molecular epidemiological survey separately. Following the α-thalassemia screening＇s diagnostic criteria which the positiveness of Hb bart, the positvie samples of Hb bart were detected the frequent deletion form genes（-SEA/, -3.7/and-4.2/） first, and the negative samples were being detected the six kinds of non deletion form＇s mutable points （α CD30, △GAT ; α CD01 , G-A ; αCD59 , G-A ; αWS , C-G ; αQS , C-G ; αCS , C-G） of a thalassemia by membrane reverse hybridization technique. The neg- ative samples of Hb bart were detected two kinds of the silent oscillation genes（ 3.7 and/-4.2/）of a thalassemia. Following the β - thalassemia screening＇s diagnostic criteria： MCV〈80 fl, H bA2〉4.0 %. 17 kinds of chinese people＇s frequent and rare β-thalassemia genes were diagnosed by PCR combined with reverrse dot blot（RDB）method if β-thalassemia＇s phenotype was positive. Results A- mong 1,000 samples of neonate cord blood, the positive rate of H b bart were 5.4 % （54/1000）. After genetic analyzed, 89 people were detected the athalassemia gene and its carrying rate of shunde were 8.9% （89/1000）. The main genotypes were SEA/aa and- a3.7/aa,the total positive rate was 89. 89%.. Among the 1100 antemarital adults, there were 43 cases which the preliminary screening＇s phenotype were positive. After genetic analyzed,all of the 43 cases carried βthalassemia gene and its detection rate was 3.91%. The most frequent mutable points of shunde were CD41-42, IVS -II- 654,-28,CD17, βE, which were 95.3 %. Conclusion The a thalassemia gene＇s carrying rate and the types of gene mutation in shunde were similar to that in the other district of Guangdong, while the β-thalassemia gene＇s carrying rate was higher than that in the other parts of Guangdong. The above results should be associated with local conditions while in the prevention.