Kesornsit Aumpika, Jeenduang Nutjaree, Horpet Dararat, Plyduang Thunyaluk, Nuinoon Manit
a School of Allied Health Sciences , Walailak University , Nakhon Si Thammarat , Thailand.
b Research Excellence Centre for Innovation and Health Products (RECIHP) , Walailak University , Nakhon Si Thammarat , Thailand.
Hemoglobin. 2018 Jan;42(1):23-29. doi: 10.1080/03630269.2018.1429281. Epub 2018 Feb 19.
Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB: c.79G>A) individuals is associated with several genetic modifiers and not well understood. This study was undertaken in order to determine the effect of single nucleotide polymorphisms (SNPs), including XmnI γ (rs7482144), rs766432 on the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying heterozygous Hb E were selected for the hematological study. After excluding the samples with α-thalassemia (α-thal) interaction or moderate anemia, because both conditions can affect the hematological parameters, the remaining 74 samples were submitted to SNP analysis. Hematological parameters were measured using an automated hematology analyzer and high performance liquid chromatography (HPLC). The results show that rs766432 was strongly associated with increased Hb F levels and rs7482144 was associated with Hb F levels in each subgroup (genotype) of rs766432. This study suggested that the BCL11A locus has a major effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes. This association of Hb F levels with SNPs is useful for the interpretation of hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future research will need to address the better understanding of the mechanisms of the SNPs that regulate Hb F production without stress erythropoiesis in Hb E heterozygotes.
杂合子Hb E（HBB：c.79G>A）个体中胎儿血红蛋白（Hb F）表达的变化与多种基因修饰因子有关，目前尚未完全明确。本研究旨在确定单核苷酸多态性（SNP），包括BCL11A基因上的XmnI γ（rs7482144）、rs766432以及HBS1L基因上的rs9376074，对泰国南部杂合子Hb E个体中Hb F水平的影响。总共选取了97名携带杂合子Hb E的泰国南部受试者进行血液学研究。在排除了存在α地中海贫血（α-thal）相互作用或中度贫血的样本后，因为这两种情况都会影响血液学参数，剩下的74个样本进行SNP分析。血液学参数使用自动血液分析仪和高效液相色谱法（HPLC）进行测量。结果显示，rs766432与Hb F水平升高密切相关，而rs7482144与rs766432的每个亚组（基因型）中的Hb F水平相关。本研究表明，与Hb E杂合子中的XmnI多态性相比，BCL11A基因座对Hb F水平有主要影响。Hb F水平与SNP的这种关联有助于解释Hb F水平高的杂合子Hb E样本中的血红蛋白（Hb）分型。未来的研究需要更好地理解在Hb E杂合子中调节Hb F产生而无应激红细胞生成的SNP机制。
