Abstract
In this study, Hb A2 variants and their association with α- and β-thalassemia (α- and β-thal) were analyzed. We performed molecular analyses to identify α-thal [– –SEA (Southeast Asian), – –THAI (Thai), –α3.7 (rightward) and –α4.2 (leftward)] deletions, and Hb Constant Spring (Hb CS; HBA2: c.427T>C), Hb A2-Melbourne (HBD: c.130G>A), Hb A2′ (HBD: c.49G>C), Hb A2-Lampang (HBD: c.142G>A). β0-Thalassemia mutations included codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (–TCTT) (HBB: c.126_129delCTTT), codons 71/72 (+A) (HBB: c.216_217insA) and IVS-I-1 (G>T) (HBB: c.92+1G>T) in 23 samples which had a Hb A2 variant peak in zone 1 of the capillary electrophoresis (CE) electropherogram. Results showed that 20 patients (87.0%) carried Hb A2-Melbourne with seven different genotypes for α- and β-thal, two (8.7%) carried Hb A2′ and one (4.3%) carried Hb A2-Lampang. All three samples doubly heterozygous for Hb A2-Melbourne/β0-thal had Hb A2 levels lower than 4.0%, while summation of Hb A2 and Hb A2-Melbourne ranged from 4.9–5.3%, reaching the accepted range (4.0–10.0%) for β-thal trait. Hb A2-Melbourne is the most common δ-globin variant in the Thai population. Hb A2 variant and Hb A2 levels must be combined in order to diagnose carriers of β-thal. β-Globin haplotype analysis showed an association with a single β-globin haplotype [+ – – – – + +] of Hb A2-Melbourne, Hb A2′ and Hb A2-Lampang, indicating that they were of the same origin. We developed a multiplex allele-specific polymerase chain reaction (ASPCR) for simultaneous detection of these three Hb A2 variants.
Acknowledgments
The authors thank Mrs. Kallayanee Treesuwan Rock, Associated Medical Sciences-Clinical Service Center, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, for refinement of the English language.
Disclosure statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.