Liu Xin, Jin Huifang, Wang Shuya, Xie Ying, Liu Xue, ChenLi Yinghui, Kong Yongkui
Department of Blood Transfusion, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Apr 10;41(4):411-416. doi: 10.3760/cma.j.cn511374-20230409-00192.
To explore the molecular basis for an individual with Bel subtype of the ABO blood type due to a novel c.620T>C variant gene, and assess its impact on the structure of GTB transferase.
An individual who had visited the First Affiliated Hospital of Zhengzhou University on February 11, 2023 was selected as the study subject. ABO phenotyping was initially conducted with serological methods, which was followed by direct sequencing of 7 exons of the ABO gene. Subsequently, single-strand sequencing was carried out by using allele-specific primers, and the variant in the B transferase was homology-modeled using the Modeller software. The impact of the variant on the transferase's spatial structure was analyzed with the PyMOL software.
The serological phenotype of the patient was identified as the Bel subtype. Direct sequencing revealed that she has harbored a novel c.620T>C variant, resulting in a p.Leu207Pro substitution in the polypeptide chain. Combined with single-strand sequencing, her genotype was ultimately determined as ABOBELnew/ABOO.01.02. Three-dimensional protein structure modeling showed that, compared with the wild type, the distance of one hydrogen bond between Proline and Glycine at position 272 has increased, along with disappearance of another hydrogen bond.
The novel c.620T>C (p.Leu207Pro) variant of B allele may affect the structural stability of the glycosyltransferase. The weakened enzyme activity in turn may lead to reduced B antigen expression, manifesting as the Bel subtype by serological analysis.
探究一名因新型c.620T>C变异基因而具有ABO血型Bel亚型个体的分子基础，并评估其对GTB转移酶结构的影响。
选取2023年2月11日就诊于郑州大学第一附属医院的一名个体作为研究对象。首先采用血清学方法进行ABO血型鉴定，随后对ABO基因的7个外显子进行直接测序。接着使用等位基因特异性引物进行单链测序，并利用Modeller软件对B转移酶中的变异进行同源建模。使用PyMOL软件分析该变异对转移酶空间结构的影响。
患者的血清学表型被鉴定为Bel亚型。直接测序显示她携带一种新型c.620T>C变异，导致多肽链中p.Leu207Pro替换。结合单链测序，其基因型最终确定为ABOBELnew/ABOO.01.02。三维蛋白质结构建模显示，与野生型相比，272位脯氨酸和甘氨酸之间一个氢键的距离增加，另一个氢键消失。
B等位基因的新型c.620T>C（p.Leu207Pro）变异可能影响糖基转移酶的结构稳定性。酶活性减弱进而可能导致B抗原表达减少，通过血清学分析表现为Bel亚型。
