Genotypic Correlation Between Six Common β-Thalassemia Mutations and the XmnI Polymorphism in the Moroccan Population

Abstract

β-Thalassemia (thal) is the most common recessive inherited disorder in Mediterranean populations. It is estimated that the frequency of this disease in the Moroccan population is between 1.5 and 3.0%. Severe forms of homozygous thalassemia cases require expensive and technically demanding curative (bone marrow transplantation) or palliative (chronic transfusion/chelation) therapies. The −158 (C→T) polymorphism of the Gγ-globin gene (XmnI polymorphism) is known to ameliorate the severity of the disease because of it strong association with an increased production of fetal hemoglobin (Hb F). Among the many known mutations in Morocco, six are common [codon 39 (C→T), frameshift codon (FSC) 8 (−AA), IVS-II-745 (C→G), FSC 6 (−A), −29 (A→G) and IVS-I-1 (G→A)]. In this study, we have investigated, in 82 Moroccan β-thalassemic chromosomes, the correlation between the six common mutations and the XmnI polymorphism using the Fisher exact test. The XmnI polymorphism was divided into two categories, (XmnI [+] and XmnI [−]) and the six common Moroccan mutations into two groups (group I with FSC 8 and group II without FSC 8). Correlation was carried out between the XmnI [+] category and the six common mutations individually that showed that 68% of chromosomes in the XmnI [+] category had the FSC 8 (−AA) mutation. The results reported here show that there is a positive correlation between the XmnI polymorphism and FSC 8 mutation in linkage with haplotype IV [− + − + + − +] (p <10−5). In conclusion, molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological Hb F switching by hydroxyurea (HU). In the Moroccan population, a good response to HU treatment should be suspected in cases with the −158 (C→T) polymorphism in linkage with haplotype IV and internal β-globin gene framework 3.