重庆地区血红蛋白病的患病率及其基因型和血液学表型分析

Prevalence, genotype and hematological phenotype analysis of hemoglobinopathy in Chongqing

摘要:

目的 分析重庆地区血红蛋白病的携带率、基因型构成及血液学特征，为血红蛋白病筛查及诊断方法的合理选择提供依据。方法 对49 551例进行血红蛋白病筛查的患者外周血样本，采用多重PCR-导流杂交或测序等方法检测地中海贫血常见23种基因位点及血红蛋白变异体（hemoglobin variants，HbVs）相关突变位点；再对确诊血红蛋白病患者的血常规和血红蛋白电泳结果进行回顾分析，评估血常规、血红蛋白电泳二者联合检查在血红蛋白病筛查诊断中的价值。结果 共检出3 511例血红蛋白病（7.09%），其中α地贫携带者1 840例，以--^SEA/αα、-α^3.7/αα和-α^4.2/αα为主；β地贫携带者1 540例，以CD17、IVS-Ⅱ-654、CD41-42为主；异常血红蛋白病65例，β链变异体为主；复合血红蛋白病64例，α地贫复合β地贫携带者57例，地贫复合异常血红蛋白病7例。血红蛋白病患者的血红蛋白、红细胞平均体积、红细胞平均血红蛋白量指标降低与α或β链合成的减少程度呈正相关，而血红蛋白A2（adult hemoglobin 2，HbA2）分别在α地贫和β地贫表现为降低和升高，或者在异常血红蛋白病中出现HbVs。单独的血常规和血红蛋白毛细管电泳筛查血红蛋白病检出率分别为84.29%和82.67%，二者联合筛查检出率可达99.11%。结论 重庆地区血红蛋白病携带者基因型具有多样性，血常规结合血红蛋白电泳是临床及产前筛查血红蛋白病的必要手段。对于筛查出HbVs的患者，出现溶血或贫血等症状时，强烈建议进行后续基因分析。

Abstract:

Objective To analyze the prevalence，genotype composition and hematological characteristics of hemoglobinopathy in Chongqing，and to reasonably select screening and diagnostic methods for hemoglobinopathy.Methods Peripheral blood samples were collected from 49 551 patients screened for hemoglobinopathy，and 23 common gene loci of thalassemia and mutations related to hemoglobin variants（HbVs） were detected by multiplex PCR-guided hybridization or sequencing. The results of routine blood test and hemoglobin electrophoresis were retrospectively analyzed to evaluate the value of the combined examination in the screening and diagnosis of hemoglobinopathy.Results A total of 3 511 cases of hemoglobinopathy were detected（7.09%）. Among them，there were 1 840 α-thalassemia and 1 540 cases of β-thalassemia gene carriers，respectively，mainly including --^SEA/αα，-α^3.7/αα，and -α^4.2/αα for α-thalassemia cases，and CD17，IVS-Ⅱ-654 and CD41-42 for β-thalassemia；there were 65 cases of abnormal hemoglobinopathy，with the majority of β-chain variants；there were 64 cases of complex hemoglobinopathy，including 57 cases of α-thalassemia combined with β-thalassemia and 7 cases of thalassemia combined with abnormal hemoglobinopathy. The decrease of hemoglobin，mean corpuscular volume and mean corpuscular hemoglobin in patients with hemoglobinopathy was positively correlated with the decrease of α or β chain synthesis，while adult hemoglobin 2（HbA2） was respectively decreased and increased in α-thalassemia and β-thalassemia，or there were HbVs in abnormal hemoglobiopathies. The detection rate of hemoglobinopathy was 84.29% and 82.67% by routine blood test and capillary electrophoresis，respectively，and the detection rate of combined screening was 99.11%.Conclusion The genotype of carriers of hemoglobinopathy in Chongqing area is diverse. Blood routine combined with Hb electrophoresis is a necessary means for clinical and prenatal screening of hemoglobinopathy. Follow-up genetic analysis is strongly recommended in patients screened for HbVs who present with symptoms such as hemolysis or anemia.