重庆地区8 024例地中海贫血筛查结果及地贫基因型分析

Screening results and genetic diagnosis of thalassemia in 8 024 cases in Chongqing region

摘要:

目的：了解重庆地区人群中α、β地中海贫血基因型的分布情况。方法：送检对象来自重庆各区、县共计8 024例样本，采用单管多重聚合酶链反应法（gap single polymeras chain reaction，GSPCR）结合反向斑点膜条杂交技术（reverse dot blot hy－bridization，RDB法）同时进行α、β地中海贫血基因检测。各组标本送检之前已在各个医院进行外周血的红细胞数（red blood cell，RBC）、血红蛋白（hemoglobin，Hb）、红细胞平均体积（mean corpuscular volume，MCV）、红细胞平均血红蛋白（mean corpuscu－lar hemoglobin，MCH）、红细胞平均血红蛋白浓度（mean corpuscular hemoglobin concentration，MCHC）细胞、血红蛋白电泳指数测定进行地中海贫血的初筛。8 024例样本男1 267例，女6 757例， 0～91岁，按年龄分为儿童组（0～16岁）317例，青壮年组（17～49岁）7 552例，老龄组（50～91岁）155例。结果：8 024例样本共检出α、β地贫111 7例，比例为13.92%。α地贫479例，其中常见缺失型α地贫基因型为--SEA/αα（332例），-α3.7/αα（84例），-α4.2/αα（15例），基因型以--SEA/αα最为常见，构成比分别为69.31％、17.54％、3.13％，共89.98％；以右缺失为主，--SEA/-α3.7 5例，--SEA/-α4.2 1例。非缺失型42例，占8.76%；确定为β地贫共619例，α复合β地贫19例。β地贫基因型本次研究中共计发现12种基因型，其中最常见的突变构成类型分别为CD17（A→T）、CD41-42（-TCTT）、IVS-2-654（C→T）、CD43、TATAboxnt-28（A→T）、βE共占96.12％，其中以CDl7（A→T）位点突变所占比例最高，CAP点突变和IVS1-1点突变各1例；8 024例样本中男性1 267例，其中地贫167例（13.18%），女性6 757例其中地贫950例（14.06%），男性和女性地贫检测阳性率差异无统计学意义（χ2=0.691，P=0.433）；男性α地贫77例，女性402例；男性β地贫74例，女性545例，男性检测为α地贫或β地贫与女性的2种地贫检测率之间的差异，无统计学意义（χ2=0.381，P=0.604）；儿童组317例确定为地贫107例（33.75%），青壮年组7 552例确定为地贫982例（13.00%），老年组155例确定地贫28例（18.06%），地贫患者各个年龄组检测阳性无统计学差异（χ2=1.711，P=0.318）。结论：重庆地区地中海贫血患者中α地中海贫血以--SEA/αα基因型最为常见，β地中海贫血则以CDl7（A→T）位点的突变最为常见。同时，青壮年组地贫的危害在于青壮年为生育年龄的集中段，所以对青壮年人群进行地贫的筛查和基因诊断，对提高人口素质有重要作用。

Abstract:

Objective：To investigate the distribution of α-& β-thalassemia in Chongqing. Methods：Totally 8 024 samples from district and counties of Chongqing were detected for α-& β-thalassemia genotype using gap single polymerase chain reaction（GSPCR） com－bined with reverse dot blot hybridization（RDB）. Before the detection，red peripheral blood cell（RBC），hemoglobin（HB），mean cor－puscular volume（MCV），mean corpuscular hemoglobin（MCH），mean corpuscular hemoglobin concentration（MCHC），hemoglobin elec－trophoresis index in each set of sample were screened. In the 8 024 samples，1 267 were male and 6 757 were female. The sample aged from 0-91 years old and were divided into chil－dren group（0-16 years old，317 cases），adult group（17-49 years old，7 572 cases） and seniors group（50-91 years old，155 cases）. Results：1 117 cases of α- and β-thalassamia were detected out from the 802 4 cases，accounting for 13.92%. Among the 1 117 cases，479 were α-thalassamia. The most common mutations were as follows：--SEA/αα（332 cases），-α3.7/αα（84 cases） and -α4.2/αα（15 cases），accounting for 89.98%，69.31%，17.54% and 3.13% respectively. Deletion a-thalassaemia was the domain type，5 cases of --SEA/-α3.7 and 1 cases of --SEA/-α4.2. There were 42 cases of non-deletional alpha-thalassaemi，accounting for 8.76%. 619 cases were surly diagnosed as β-thalassamia and 19 cases were α-thalassemia composite β-thalassamia. 12 β-thalassamia genotypes were found，and the common constitutions of mutation were CD17（A→T）（the most common constitution），CD41—42（-TCTT），IVS-2-654（C→T），CD43，TATAboxnt -28（A→T），βE，accounting for 96.12%. There was 1 case CAP and 1 case IVS1-1. Among the 8 024 cases，167 male cases and female 950 cases were diagnosed as α-& β-thalassemia including 77 male cases and 402 female cases of α-tha－lassemia as well as 74 male cases and 545 female cases of β-thalassemia. The positive rate of α-& β-thalassemia was higher in fe－male than in male，but having no statistical significance（ χ2=0.691，P=0.433）. There was no statistical significance in detection rate of α-& β-thalassemia between male and female（ χ2=0.381，P=0.604）. Among all samples，317（33.75%） cases in children group，982（13.00%） cases in adult group and 155（18.06%） cases in senior group were diagnosed as thalassemia（ χ2=1.711，P=0.318），without statistical differences. Conclusions：--SEA/αα genotype and CD17（A→T） gene mutation is the most common type in α-thalassemia and β-thalassemia in Chongqing. However，the significant hazard in adult group concentrates in the breeding age. Thus to screen tha－lassemia genotype of adult in breeding age is of great significance in raising population quality.