BackgroundHemoglobin Constant Spring (Hb CS) is an abnormal Hb caused by a mutation at the termination codon of α2-globin gene found commonly among Southeast Asian and Chinese people. Association of Hb CS with α°-thalassemia leads to a thalassemia intermedia syndrome commonly encountered in the region. We report chromosome background and addressed genetic origins of Hb CS observed in a large cohort of Hb CS among Southeast Asian populations.Materials and MethodsA study was done on 102 Vietnamese (aged 15–49 year-old) and 40 Laotian (aged 18–39 year-old) subjects with Hb CS and results compared with 120 Hb CS genes in Thailand. Hematological parameters were recorded and Hb analysis was performed using capillary electrophoresis. Hb CS mutation and thalassemia genotypes were defined by DNA analysis. Six DNA polymorphisms within α-globin gene cluster including 5’Xba I, Bgl I, Inter-zeta HVR, AccI, RsaI and αPstI 3’, were determined using PCR-RFLP assay.ResultsNine different genotypes of Hb CS were observed. In contrast to the Thai Hb CS alleles which are mostly linked to haplotype (+—S + + -), most of the Vietnamese and the Laotian Hb CS genes were associated with haplotype (+—M + + -), both of which are different from that of the European Hb CS.ConclusionsHb CS is commonly found in combination with other thalassemias among Southeast Asian populations. Accurate genotyping of the cases requires both hematologic and DNA analyses. At least two independent origins are associated with the Hb CS gene which could indirectly explain the high prevalence of this Hb variant in the region.

Haemoglobin (Hb) E is the most common Hb variant in Asia where its gene frequency approaches 0.3 in some areas. We studied genetic background of Hb E genes among Southeast Asian populations. This study examined β-globin gene haplotypes linked to haemoglobin E (Hb E) in diverse groups of Southeast Asian populations. The study was conducted on southern Thai (22 alleles), Cambodian (84 alleles), Laotian (120 alleles), Vietnamese (87 alleles) and Burmese (one allele) subjects. Results were compared with those of previous studies in northeast Thailand, the Yunnan of China, West India and Europe. Ten different haplotypes were observed. The four most common haplotypes were haplotypes 1 (- + - + + + -) and 2 (+ - - - - + -) on chromosomes with framework 2 and haplotypes 6 (- + - + + - +) and 7 (+ - - - - - +) on chromosomes with framework 3 variety. Phylogenetic analysis indicated that haplotype 1 is a relatively recent haplotype found in all populations, whereas haplotype 6 is found predominately in Cambodians. The results indicate that at least two genetic origins of Hb E are responsible for the high prevalence and spread of Hb E among Southeast Asian populations.

No abstract

IC strip assay for ζ-globin is simple, rapid and does not require sophisticated equipment. Use of this test in addition to the existing screening protocol could detect potential (--) α-thalassaemia leading to a significant reduction in the workload of DNA analysis. This could be used in areas where haemoglobinopathies are prevalent and heterogeneous but molecular testing is not available.