中国人群血型ABO亚型的分子基础研究

doi:10.16150/j.1671-2870.2020.04.008

摘要/Abstract

摘要：

目的： 对我国人群血型ABO亚型的表型与基因型进行关联性研究,以探讨ABO亚型的分布特点及分子背景。方法： 采用血清学方法对2014年7月至2019年6月间1 545 505名献血者和116 209例受血者中检出的血型ABO亚型进行表型鉴定,用直接测序或克隆后测序分析ABO基因的DNA序列。结果： 血型血清学鉴定在1 545 505名献血者和116 209例受血者中共检出ABO亚型617例,检出率为3.71/万,检出率最高的表型为B（A）（0.066‰）,其次是B₃（0.045‰）和B_x（0.039‰）。544例ABO亚型样本经基因测序鉴定出42种ABO亚型等位基因,其中ABO*BA.04的检出构成比最高（25.20%）,其次为ABO*BA.02 （11.55%）和ABO*cis-AB.01（9.71%）。关联分析提示,ABO亚型等位基因所对应的表型可与首次检测的表型不一致,即一种基因型可对应多种表型。结论： 中国人群血型ABO亚型检出率为3.71/万,B(A)表型是中国人群中最常检出的ABO亚型,B₃和B_x相关的亚型次之;较常检出的亚型等位基因则是ABO*BA.04、ABO*BA.02和ABO*cis-AB.01。

关键词: ABO亚型, 基因突变, 等位基因

Abstract:

Objective: To explore distribution and molecular basis of ABO blood subgroups in Chinese population by analyzing phenotype-genotype correlations of ABO subgroups. Methods: Phenotype investigations were performed using serology studies in 1 545 505 blood donors and 116 209 blood recipients enrolled from April 2014 to June 2019, and the DNA sequence of the ABO gene was analyzed by direct sequencing or sequencing after cloning. Results: Serologic typing revealed that ABO subgroup were detected in 617 individuals, with an overall incidence of 3.71/10 000. Subgroup B(A) showed the highest detection rate(0.066‰), and was followed by B₃(0.045‰) and B_x (0.039‰). A total of 42 ABO subgroup alleles were identified in 544 individuals by direct sequencing. According to the results of sequencing, ABO*BA.04 was the most common allele, with a constituent ratio of 25.20%, and then ABO*BA.02(11.55%) and ABO*cis-AB.01(9.71%). Correlation analysis revealed that corresponding phenotype of ABO subgroup alleles might differ from result of first testing, which meant a certain genotype could show multiple different phenotypes. Conclusions: Incidence of ABO blood subgroups in Chinese population is 3.71/10 000. B(A) subgroup is the most common in Chinese population and followed by B₃ and B_x related subgroups. The common subgroup alleles are ABO*BA.04,BA.02 and cis-AB.01.

Key words: ABO subgroup, Gene mutation, Allele

中图分类号:

R446.11

雷航, 范亮峰, 蔡晓红, 王钰箐, 刘曦, 金沙, 沈伟, 陆琼, 向东, 王学锋, 邹纬. 中国人群血型ABO亚型的分子基础研究[J]. 诊断学理论与实践, 2020, 19(04): 364-369.

LEI Hang, FAN Liangfeng, CAI Xiaohong, WANG Yuqing, LIU Xi, JIN Sha, SHEN Wei, LU Qiong, XIANG Dong, WANG Xuefeng, ZOU Wei. The study on molecular basis of ABO blood subgroups in the Chinese population[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(04): 364-369.

图/表 3

表1

图1

表2

本研究中检出的42种ABO亚型等位基因

编号	等位基因	关键核苷酸改变^*	个体(家系)	血清型	基因型
1	A3.09	c.1A>G	2	A₃	A3.09/O.01.01
2	AW.31.01	c.297A>G c.646T>A c.681G>A c.771C>T c.829G>A	2	A_elB	AW.31.01/B.01
3	A2.17	c.407C>T	2	A_x	A2.17/O.01.02
4	AW.38	c.426G>C	2	A_x	AW.38/O.0102
5	A2.08	c.539G>C	3	A_xB	A2.08/B.01
6	AW.30	c.565A>G	2	A_mB	AW.30/B.01
7	AW.31.02-05	c.646T>A c.681G>A c.771C>T c.829G>A	2	A_x	AW.31.02-05/O.01.02
8	AEL.02	c.646T>A c.681G>A	2	A_el	AEL.02/O.01.01
9	A3.07	c.742C>T	5	A_m, A_el, A_x,B	A3.07/O.01.01
10	AEL.05	c.767T>C	2	A_el	AEL.05/O.01.02
11	cis-AB.01	c.803G>C	37	A₂B_x, AB_x, A₂B	cis-AB.01/O.01.01, cis-AB.01/O.01.02, cis-AB.01/B.01
12	AEL.08	c.804insG	2	A_el	AEL.08/O.01.02
13	cis-AB01var	c.803G>C c.1009A>G	2(1)	A_xB_x	cis-AB01var/O.01.01, cis-AB01var/B.01
14	A2.05	c.1009A>G	15	A₂, A_int, A₂B, A_intB,A_x, A_el,A_elB	A2.05/B.01, A2.05/O.01.01, A2.05/O.01.02
15	A2.01	c.1061delC	7	A₂B,A_xB	A2.01/B.01
16	Avar-2	c.700C>A	2	A_x	Avar-2/O.01.01
17	Avar-4	c.963insC	2	A_el	Avar-4/O.01.01
18	Avar-5	c.964G>A	2	A_end	Avar-5/O.01.01
19	Avar-6	c.106T>C	2	A_xB	Avar-6/B.01
20	B3.11	35_-18del	12	B_x, B₃,AB₃	B3.11/O.01.01,A1.02/B3.11
21	B3.10	c.28G>A	2	B_end	B3.10/O.01.02
22	B3.04	c.247G>T	2	AB₃	A1.02/B3.04
23	BW.12	c.278C>T	22	B_x, B_m, AB_x, AB_m, AB₃	BW.12/O.01.01,BW.12/O.01.02,A1.01/BW.12
24	B3.05	c.425T>C	18	B_x,AB_x,B_m	B3.05/O.01.01,A1.01/B3.05
25	BEL.03	c.502C>T	3	B_el	BEL.03/O.01.02
26	BW.22	c.503G>A	2	AB_x	A1.02/BW.22
27	cis-AB.06	c.526G>C	2	A_xB	cis-AB.06/O.01.01
28	BW.19	c.646T>A c.681G>A	3	AB_x	A1.02/BW.19
29	BW.11	c.695T>C	7	B_x	BW.11/O.01.01,BW.11/O.01.02
30	cis-AB.03	c.700C>T	2	A₂B_x	cis-AB.03/O.01.02
31	BA.04	c.640A>G	96	B(A)	BA.04/O.0101,BA.04/O.01.02,BA.04/B1.01
32	BA.02	c.700C>G	44(2)	AB_x,B(A)	A1.02/BA.02,BA.02/O.01.01BA.02/O.01.02, BA.02/B1.01
33	BW.03	c.721C>T	25	B_x,B_x,B_m	BW.03/O.01.01,A1.02/BW.03
34	cis-AB.02	c.796A>C	5	A2B_x,AB_x	cis-AB.02/O.01.02, cis-AB.02/A1.02
35	BA.06	c.803C>G	7	A_xB,B(A)	A1.02/BA.06,BA.06/O.01.01BA.06/O.01.02, BA.06/B1.01
36	BW.34	c.889G>A	2	AB_x	BW.34/O.01.02
37	BW.27	c.905A>G	17	B_x	BW.27/O.01.01
38	BW.07	c.1055G>A	5	AB_x	A1.02/BW.07
39	Bvar-1	c.523G>A c.746G>A	7	B_x	Bvar-1/O.01.01
40	B3.02	c.646T>A	2	AB₃	B3.02/A1.02
41	Bvar-3	c.664G>A	5	B_x,B₃	Bvar-3/O.01.01
42	Bx11	c.538C>T	2	AB_w	A1.02/Bx11

表2

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来源	总检测数（n）	亚型检出数（n）	检出率（万）
献血者	1 545 505	590	3.82
门急诊患者	116 209	27	2.32
总计	1 661 714	617	3.71