广西不孕不育人群α-地中海贫血基因分型与筛查结果分析
|
摘要
目的调查广西不孕不育人群α-地中海贫血的携带率、基因分型及基因频率,分析三种α-地贫表型与非地贫人群血液学参数及血红蛋白电泳结果之间关系。方法通过排除HbA_2>3.5%和(或)HbF>2%者可能为β-地贫人群,纳入2017-2018年来我中心就诊的10 020例不孕不育者进行α-地贫基因检测,对三种α-地贫表型血液学参数及血红蛋白电泳结果比较分析。结果共确诊α-地贫624例,19种基因型,总携带率为6.23%,其中静止型275例(2.74%),轻型326例(3.25%),中间型23例(0.23%),最常见为--~(SEA)/αα,其次为-α~(3.7)/αα和α~(CS)α/αα。三种α-地贫表型MCV、MCH、MCHC、Hb、HCT和HbA_2均低于非地贫人群,而RBC均高于非地贫人群(均P<0.05)。上述参数(HbA_2除外)均表现为静止型>轻型>中间型,RBC在静止型、轻型和中间型呈逐渐增高趋势。结论广西不孕不育人群α-地贫患病率较高,--~(SEA)/αα为最常见基因型,MCV、MCH、MCHC、Hb、RBC和HCT有助于不孕不育人群α-地贫筛查,对区分三种α-地贫表型有一定临床价值。
Objective Investigation of the carrier rate, genotyping and genotype frequency of alpha-thalassemia among infertile subjects in Guangxi, and analysis of the relationship between the results of hemoglobin electrophoresis and hematologic parameters among patients with three phenotypes of alpha-thalassemia and subjects with non-thalassemia. Methods The preliminarily patients who were diagnosed as beta-thalassemia via HbA2 >3.5% and/or HbF > 2% were excluded. Alpha-thalassemia genes of 10 020 infertile subjects were detected in our center from 2017 to 2018, and the results of hemoglobin electrophoresis and hematologic parameters in patients with three phenotypes of alpha-thalassemia were compared. Results 624 patients with alpha-thalassemia were confirmed via gene diagnostic technique, including 19 genotypes, total carrier rate for 6.23%, 275(2.74%) patients with silent alpha-thalassemia, 326(3.25%) patients with alpha-thalassemia trait and 23(0.23%) patients with HbH disease. The most common genotype was--SEA/αα, followed by-α3.7/αα and α, CSα/αα. The parameters of MCV,MCH, MCHC, Hb, HCT, HbA2 were lower, but the value of RBC were higher(both P < 0.05), in patients with three phenotypes of alpha-thalassemia than subjects with non-thalassemia. The parameters mentioned above excluding HbA2 in patients with alpha-thalassemia showed the following regularity : silent alpha-thalassemia > potential alpha-thalassemia > HbH disease. RBC value tended to increase gradually in patients with silent alpha-thalassemia,potential alpha-thalassemia and HbH disease. Conclusion Infertility with alpha-thalassemia is very popular in Guangxi, especially--SEA/αα which is the most common genotype. The value of MCV, MCH, MCHC, Hb, RBC and HCT are conducive to screening for infertile subjects with alpha-thalassemia, and have certain clinical value for differentiating three phenotypes of alpha-thalassemia.
Objective Investigation of the carrier rate, genotyping and genotype frequency of alpha-thalassemia among infertile subjects in Guangxi, and analysis of the relationship between the results of hemoglobin electrophoresis and hematologic parameters among patients with three phenotypes of alpha-thalassemia and subjects with non-thalassemia. Methods The preliminarily patients who were diagnosed as beta-thalassemia via HbA2 >3.5% and/or HbF > 2% were excluded. Alpha-thalassemia genes of 10 020 infertile subjects were detected in our center from 2017 to 2018, and the results of hemoglobin electrophoresis and hematologic parameters in patients with three phenotypes of alpha-thalassemia were compared. Results 624 patients with alpha-thalassemia were confirmed via gene diagnostic technique, including 19 genotypes, total carrier rate for 6.23%, 275(2.74%) patients with silent alpha-thalassemia, 326(3.25%) patients with alpha-thalassemia trait and 23(0.23%) patients with HbH disease. The most common genotype was--SEA/αα, followed by-α3.7/αα and α, CSα/αα. The parameters of MCV,MCH, MCHC, Hb, HCT, HbA2 were lower, but the value of RBC were higher(both P < 0.05), in patients with three phenotypes of alpha-thalassemia than subjects with non-thalassemia. The parameters mentioned above excluding HbA2 in patients with alpha-thalassemia showed the following regularity : silent alpha-thalassemia > potential alpha-thalassemia > HbH disease. RBC value tended to increase gradually in patients with silent alpha-thalassemia,potential alpha-thalassemia and HbH disease. Conclusion Infertility with alpha-thalassemia is very popular in Guangxi, especially--SEA/αα which is the most common genotype. The value of MCV, MCH, MCHC, Hb, RBC and HCT are conducive to screening for infertile subjects with alpha-thalassemia, and have certain clinical value for differentiating three phenotypes of alpha-thalassemia.
引文
[1]LAI K,LI S,LIN W,et al.Invasive prenatal diagnosis of alphathalassemia to control Hb Bart′s hydrops fetalis syndrome:15years of experience[J].Arch Gynecol Obstet,2018,298(2):307-311.
[2]LAI K,HUANG G,SU L,et al.The prevalence of thalassemia in mainland China:evidence from epidemiological surveys[J].Sci Rep,2017,7(1):920.
[3]TRAEGER-SYNODINOS J,HARTEVELD C L,OLD J M,et al.EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies[J].Eur J Hum Genet,2015,23(4):426-437.
[4]VELASCO-RODRIGUEZ D,BLAS C,ALONSO-DOMINGUEZJ M,et al.Cut-Off values of hematologic parameters to predict the number of alpha genes deleted in subjects with deletional alpha thalassemia[J].Int J Mol Sci,2017,18(12).
[5]XIE X M,ZHOU J Y,LI J,et al.Implementation of newborn screening for hemoglobin h disease in mainland china[J].Indian J Hematol Blood Transfus,2015,31(2):242-246.
[6]VICHINSKY E P.Clinical manifestations of alpha-thalassemia[J].Cold Spring Harb Perspect Med,2013,3(5):a011742.
[7]FARASHI S,HARTEVELD C L.Molecular basis of alpha-thalassemia[J].Blood Cells Mol Dis,2018,70:43-53.
[8]HE S,QIN Q,YI S,et al.Prevalence and genetic analysis of alpha-and beta-thalassemia in Baise region,a multi-ethnic region in southern China[J].Gene,2017,619:71-75.
[9]马升俊,肖永君,韦子斌.广西南宁地区不孕不育患者地中海贫血检查结果分析[J].中国优生与遗传杂志,2013,21(03):35-36,118.
[10]XU C,LIAO B,QI Y,et al.Analysis of gene mutation types of alpha-and beta-Thalassemia in Fuzhou,Fujian Province in China[J].Hemoglobin,2018,42(3):143-147.
[11]王丽娟,朱元昌,尹彪,等.深圳地区不孕不育患者α、β地中海贫血分子流行病学回顾性分析[J].中国优生与遗传杂志,2013,21(2):17-19.
[12]赵芳,何小洪,程静,等.广州地区1571例胎儿地中海贫血产前基因型与血液学特征分析[J].实用医学杂志,2016,32(21):3562-3565.
[13]裴元元,冉健,魏凤香.深圳地区学龄前儿童贫血状况及地中海贫血基因突变类型[J].实用医学杂志,2017,33(1):131-133.
[2]LAI K,HUANG G,SU L,et al.The prevalence of thalassemia in mainland China:evidence from epidemiological surveys[J].Sci Rep,2017,7(1):920.
[3]TRAEGER-SYNODINOS J,HARTEVELD C L,OLD J M,et al.EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies[J].Eur J Hum Genet,2015,23(4):426-437.
[4]VELASCO-RODRIGUEZ D,BLAS C,ALONSO-DOMINGUEZJ M,et al.Cut-Off values of hematologic parameters to predict the number of alpha genes deleted in subjects with deletional alpha thalassemia[J].Int J Mol Sci,2017,18(12).
[5]XIE X M,ZHOU J Y,LI J,et al.Implementation of newborn screening for hemoglobin h disease in mainland china[J].Indian J Hematol Blood Transfus,2015,31(2):242-246.
[6]VICHINSKY E P.Clinical manifestations of alpha-thalassemia[J].Cold Spring Harb Perspect Med,2013,3(5):a011742.
[7]FARASHI S,HARTEVELD C L.Molecular basis of alpha-thalassemia[J].Blood Cells Mol Dis,2018,70:43-53.
[8]HE S,QIN Q,YI S,et al.Prevalence and genetic analysis of alpha-and beta-thalassemia in Baise region,a multi-ethnic region in southern China[J].Gene,2017,619:71-75.
[9]马升俊,肖永君,韦子斌.广西南宁地区不孕不育患者地中海贫血检查结果分析[J].中国优生与遗传杂志,2013,21(03):35-36,118.
[10]XU C,LIAO B,QI Y,et al.Analysis of gene mutation types of alpha-and beta-Thalassemia in Fuzhou,Fujian Province in China[J].Hemoglobin,2018,42(3):143-147.
[11]王丽娟,朱元昌,尹彪,等.深圳地区不孕不育患者α、β地中海贫血分子流行病学回顾性分析[J].中国优生与遗传杂志,2013,21(2):17-19.
[12]赵芳,何小洪,程静,等.广州地区1571例胎儿地中海贫血产前基因型与血液学特征分析[J].实用医学杂志,2016,32(21):3562-3565.
[13]裴元元,冉健,魏凤香.深圳地区学龄前儿童贫血状况及地中海贫血基因突变类型[J].实用医学杂志,2017,33(1):131-133.