Rujito Lantip, Basalamah Muhammad, Siswandari Wahyu, Setyono Joko, Wulandari Gondo, Mulatsih Sri, Sofro Abdul Salam M, Sadewa Ahmad Hamim, Sutaryo Sutaryo
Department of Molecular Biology, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia.
Department of Pediatrics, Banyumas General Hospital, Banyumas, Central Java, Indonesia.
Hematol Oncol Stem Cell Ther. 2016 Jun;9(2):55-63. doi: 10.1016/j.hemonc.2016.02.003. Epub 2016 Mar 17.
OBJECTIVE/BACKGROUND: Thalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin (HbF) production has been reported as an influencing phenotypic factor of β-thalassemia (β-thal). Therefore, this study aimed to find the effect of these genetic modifiers, especially in the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB), among β-thal and HbE/β-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among β-thal and HbE/β-thal patients in Indonesia.
A total of 189 patients with genotyping of β-thal and HbE/β-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of β-thal and HbE/β-thal was classified based on the Mahidol score. Polymorphism of the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS) methods.
The distributions of minor allele in the XmnI locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the XmnI locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE/β-thal patients, but rs9399137 did not demonstrate such features. In β-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance.
The XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/β-thal patients in Indonesia, but not in β-thal patients.
目的/背景：地中海贫血是一种单基因血液疾病，在全球范围内患病率最高。此外，患者中存在与多种表型相关的复杂遗传背景。据报道，与胎儿血红蛋白（HbF）产生相关的遗传异质性是β地中海贫血（β-地贫）的一个影响表型因素。因此，本研究旨在根据实验室和临床结果，包括HbF水平和临床评分，探究这些遗传修饰因子，特别是XmnI位点、rs11886868、rs766432（BCL11A）和rs9399137（HBS1L-MYB）在印度尼西亚β-地贫和HbE/β-地贫患者中的作用。本研究还旨在比较印度尼西亚β-地贫和HbE/β-地贫患者之间的这些修饰作用。
本研究共纳入189例进行了β-地贫和HbE/β-地贫基因分型的患者。采用适当方法计算红细胞指数和Hb电泳测量值。根据玛希隆评分对β-地贫和HbE/β-地贫的严重程度进行分类。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和扩增阻滞突变系统（ARMS）方法确定XmnI位点、rs11886868、rs766432（BCL11A）和rs9399137（HBS1L-MYB）的多态性。
XmnI位点（rs11886868）、rs766432和rs9399137的次要等位基因分布分别为14%、22%、19%和18%。XmnI位点、rs11886868和rs766432中的变异等位基因在HbE/β-地贫患者中对修饰HbF和临床评分具有显著意义，但rs9399137未显示出此类特征。然而，在β-地贫患者中，未发现任何单核苷酸多态性与临床表现之间存在相关性。
XmnI位点、rs11886868和rs766432对印度尼西亚HbE/β-地贫患者的HbF和临床评分具有修饰作用，但对β-地贫患者无此作用。
