血液学指标在中国福建地区α-地中海贫血筛查中的价值
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摘要
目的:分析福建省不同地区α-地中海贫血的基因类型与构成比,比较相应的血液学表型特征,探讨平均红细胞体积(MCV)、平均红细胞血红蛋白量(MCH)、血红蛋白量(Hb)、红细胞分布宽度/红细胞计数(RDW/RBC)对该地区α地中海贫血初筛的价值。方法:通过Gap-PCR法检测α地中海贫血缺失型突变,反向点杂交法检测非缺失型突变位点,对α地中海贫血基因型进行分型确定,并分析确诊的α地中海贫血患者血液学数据,通过分析ROC曲线确定本地区α地中海贫血的最佳截断值,分析血液学指标在α地中海贫血中的筛查价值。结果:纳入的772例α地中海贫血患者中,共发现16种基因突变类型,以--SEA/αα缺失型突变最为常见(67.49%,521/272)。与对照组相比,同性别不同分型的患者MCV、MCH、Hb的均值差异均有统计学意义,而RDW/RBC值在男性患者中标准型和HbH病2组与对照组相比差异有统计学意义,女性α地中海贫血患者中仅有HbH病组与对照组差异有统计学意义。MCV<81.25 fl、MCH<27.30 pg、Hb_(男性)<128.5 g/L, Hb_(女性)<123.5 g/L为本实验室α地中海贫血的最佳截断值,具有较高的特异性与敏感性。结论:由于地域异质性以及各个医院设备环境的不同,不同实验室应建立适宜本地区的α地中海贫血初筛截断值。今后本实验室可选择MCV<81.25 fl、MCH<27.30 pg、Hb男性<128.5 g/L、Hb女性<123.5 g/L作为临床筛查α地中海贫血初筛值。
Objective: To analyze the genotypes and the hematological phenotypic characteristics of α-thalassemia in different areas of Fujian and to evaluate the values of mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), hemoglobin(Hb), RBC distribution width/red blood cell(RDW/RBC) for screening α-thalassemia in this area. Methods: The Gap-PCR assay was applied for detecting 3 common deletional mutations of patients with α-thalassemia, and the reverse dot-blot(RDB) assay was adopted to detect the foci of 3 common non-deletional gene mutations.Then,the hematological parameters of individuals with α-thalassemia were analyzed. Finally, the optimal cut-off value in hematological indexes for screening α-thalassemia were determined by the ROC curve. Results: Altogether 16 types of gene mutations were found in 772 patients with α-thalassemia. Among them, the-SEA/αα deletion mutation was the most common which was observed in 521 cases(67.49%). Compared with the control group, the differences in MCV, MCH, and Hb were statistically significant between the patients of the same sex but no same type. In male groups, the RDW/RBC ratio was statistically significant in individuals of light type and HbH disease as compared with the healthy control group. But in female groups, the statistical different of RDW/RBC ratio was found between only HbH disease group and control group. MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L, with the highest specificity and the highest sensitivity, were the best cut-off points for screening α-thalassemia in the laboratory. Conclusion: Due to the difference of regional heterogeneity and hospital equipment environment, the different laboratories need to establish cut-off value for screening α-thalassemia suitable for its local region. In future, our laboratory can use MCV<81.25 fl, MCH <27.30 pg, Hb(male) <128.5 g/L, and Hb(female) <123.5 g/L for value for clinical screening, of α-thalassemia.
Objective: To analyze the genotypes and the hematological phenotypic characteristics of α-thalassemia in different areas of Fujian and to evaluate the values of mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), hemoglobin(Hb), RBC distribution width/red blood cell(RDW/RBC) for screening α-thalassemia in this area. Methods: The Gap-PCR assay was applied for detecting 3 common deletional mutations of patients with α-thalassemia, and the reverse dot-blot(RDB) assay was adopted to detect the foci of 3 common non-deletional gene mutations.Then,the hematological parameters of individuals with α-thalassemia were analyzed. Finally, the optimal cut-off value in hematological indexes for screening α-thalassemia were determined by the ROC curve. Results: Altogether 16 types of gene mutations were found in 772 patients with α-thalassemia. Among them, the-SEA/αα deletion mutation was the most common which was observed in 521 cases(67.49%). Compared with the control group, the differences in MCV, MCH, and Hb were statistically significant between the patients of the same sex but no same type. In male groups, the RDW/RBC ratio was statistically significant in individuals of light type and HbH disease as compared with the healthy control group. But in female groups, the statistical different of RDW/RBC ratio was found between only HbH disease group and control group. MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L, with the highest specificity and the highest sensitivity, were the best cut-off points for screening α-thalassemia in the laboratory. Conclusion: Due to the difference of regional heterogeneity and hospital equipment environment, the different laboratories need to establish cut-off value for screening α-thalassemia suitable for its local region. In future, our laboratory can use MCV<81.25 fl, MCH <27.30 pg, Hb(male) <128.5 g/L, and Hb(female) <123.5 g/L for value for clinical screening, of α-thalassemia.
引文
1 Li B,Zhang XZ,Yin AH,et al.High prevalence of thalassemia in migrant populations in Guangdong Province.China.BMC Public Health,2014;14:905.
2 Li CK.New trend in the epidemiology of thalassaemia.Best Pract Res Clin Obstet Gynaecol,2017;39:16-26.
3 Ferr?o J,Silva M,Gon?alves L,et al.Widening the spectrum of deletions and molecular mechanisms underlying AlphaThalassemia.Ann Hematol,2017;96(11):1921-1929.
4 Koh DXR,Raja Sabudin RZA,Mohd Yusoff M,et al.Molecular characterisation ofα-andβ-thalassaemia among indigenous senoi orang Asli communities in Peninsular Malaysia.Ann Hum Genet,2017;81(5):205-212.
5 Weatherall DJ.Thalassemia as a global health problem:recent progress toward its control in the developing countries.Ann N YAcad Sci,2010;1202:17-23.
6杨阳,张杰.中国南方地区地中海贫血研究进展.中国实验血液学杂志,2017;25(01):276-280.
7 Xu XM,Zhou YQ,Luo GX,et al.The prevalence and spectrum of Alpha and Beta Thalassaemia in Guangdong Province:implications for the future health burden and population screening.J Clin Pathol,2004;57(5):517-522.
8 Lin M,Zhong TY,Chen YG,et al.Molecular Epidemiological Characterization and health burden of thalassemia in Jiangxi Province,P.R.China.PLoS One,2014;9(7):e101505.
9 Yin XL,Wu ZK,He YY,et al.Treatment and complications of thalassemia major in Guangxi,Southern China.Pediatr Blood Cancer,2011;57(7):1174-1178.
10.Huang YJ,Wu SG,Ou XB,et al.Changes of iron metabolism indices in children with various genotypes of thalassema.Zhongguo Dang Dai Er Ke Za Zhi,2010;12(2):85-88.
11.Harteveld CL,Higgs DR.Alpha-thalassaemia.Orphanet J Rare Dis,2010;5:13.
12.Luo JL,Chen XD.Genotype of Patients withαandβThalassemia in Northern Area of Fujian Province in China.中国实验血液学杂志,2016;24(2):540-545.
13.冉健,裴元元,魏凤香,等.深圳地区α-地中海贫血及αβ-复合地中海贫血的相关性研究.中国妇幼保健,2016;31(7):1468-1471.
14.宇传华,余松林.医学统计学.北京.人民卫生出版社.2002;164-178.
15.Cappellini MD,Cohen A,Porter J,et al.Guidelines for the management of transfusion dependent thalassaemia(TDT)[Internet].3rd edition.Nicosia(CY):Thalassaemia International Federation;2014.
2 Li CK.New trend in the epidemiology of thalassaemia.Best Pract Res Clin Obstet Gynaecol,2017;39:16-26.
3 Ferr?o J,Silva M,Gon?alves L,et al.Widening the spectrum of deletions and molecular mechanisms underlying AlphaThalassemia.Ann Hematol,2017;96(11):1921-1929.
4 Koh DXR,Raja Sabudin RZA,Mohd Yusoff M,et al.Molecular characterisation ofα-andβ-thalassaemia among indigenous senoi orang Asli communities in Peninsular Malaysia.Ann Hum Genet,2017;81(5):205-212.
5 Weatherall DJ.Thalassemia as a global health problem:recent progress toward its control in the developing countries.Ann N YAcad Sci,2010;1202:17-23.
6杨阳,张杰.中国南方地区地中海贫血研究进展.中国实验血液学杂志,2017;25(01):276-280.
7 Xu XM,Zhou YQ,Luo GX,et al.The prevalence and spectrum of Alpha and Beta Thalassaemia in Guangdong Province:implications for the future health burden and population screening.J Clin Pathol,2004;57(5):517-522.
8 Lin M,Zhong TY,Chen YG,et al.Molecular Epidemiological Characterization and health burden of thalassemia in Jiangxi Province,P.R.China.PLoS One,2014;9(7):e101505.
9 Yin XL,Wu ZK,He YY,et al.Treatment and complications of thalassemia major in Guangxi,Southern China.Pediatr Blood Cancer,2011;57(7):1174-1178.
10.Huang YJ,Wu SG,Ou XB,et al.Changes of iron metabolism indices in children with various genotypes of thalassema.Zhongguo Dang Dai Er Ke Za Zhi,2010;12(2):85-88.
11.Harteveld CL,Higgs DR.Alpha-thalassaemia.Orphanet J Rare Dis,2010;5:13.
12.Luo JL,Chen XD.Genotype of Patients withαandβThalassemia in Northern Area of Fujian Province in China.中国实验血液学杂志,2016;24(2):540-545.
13.冉健,裴元元,魏凤香,等.深圳地区α-地中海贫血及αβ-复合地中海贫血的相关性研究.中国妇幼保健,2016;31(7):1468-1471.
14.宇传华,余松林.医学统计学.北京.人民卫生出版社.2002;164-178.
15.Cappellini MD,Cohen A,Porter J,et al.Guidelines for the management of transfusion dependent thalassaemia(TDT)[Internet].3rd edition.Nicosia(CY):Thalassaemia International Federation;2014.