HBG2 -158 (C>T) polymorphism and its contribution to fetal hemoglobin variability in Iraqi Kurds with beta-thalassemia minor

Abstract

PURPOSE: Hemoglobin (Hb) F% is increased in up to half of beta-thalassemia (β-thal) carriers. Several polymorphisms have been linked to such variability in different populations, including HBG2 - 158(C>T) (Xmn I polymorphism) on chromosome 11. To determine the role of this polymorphism in such variability among Iraqi Kurds, the current study was initiated. MATERIALS AND METHODS: A total of 102 consecutive patients diagnosed as β-thal minor were enrolled. The enrollees had their diagnosis based on peripheral blood counts and high-performance liquid chromatography to determine HbA2 and HbF. All enrollees had their DNA extracted by phenol-chloroform method and Xmn I polymorphism detected by restriction fragment length polymorphism-polymerase chain reaction. RESULTS: The mean age (standard deviation [SD]) of the 102 enrollees was 25.4 (14.0) years, and the enrollees included 48 males and 54 females. Xmn I polymorphism was identified in heterozygous state in 46 (45.1%) patients and in homozygous state in one patient (0.98%). Thus, the minor allele frequency of this polymorphism was 0.235 in the studied group. There were no significant differences in red cell indices and HbA2% in carriers of the minor allele compared to noncarriers, while HbF% and absolute HbF concentrations were significantly higher in the former subgroup (P = 0.032 and 0.014, respectively). This polymorphism's contribution to HbF variability was found to be 5.8% in the studied sample. Furthermore, those with HbF ≥2% were 3.2 folds more likely to carry the minor allele. CONCLUSIONS: Xmn I polymorphism is frequently encountered in Iraqi Kurds with β-thal minor, and it is significantly associated with higher fetal hemoglobin in these patients.

Risk Association, Linkage Disequilibrium, and Haplotype Analyses of β-Like Globin Gene Polymorphisms with Malaria Risk in the Sabah Population of Malaysian Borneo

“…Variants in a human gene are regularly associated with the risk of certain diseases. For example, the C-158T (rs7482144) single nucleotide polymorphism (SNP) in the 5′ region of the hemoglobin subunit gamma 2 gene is linked with higher fetal hemoglobin levels, sickle cell anemia, and thalassemia [ 7 , 8 ]. Interestingly, another SNP in the 5′ region of the β-globin gene, the C-551T (rs number is not available), is found as a silencer for the gene’s transcription and is associated with a thalassemic phenotype [ 9 ].…”