A Large Cohort of Hemoglobin Variants in Thailand: Molecular Epidemiological Study and Diagnostic Consideration

Abstract

BackgroundHemoglobin (Hb) variants are structurally inherited changes of globin chains. Accurate diagnoses of these variants are important for planning of appropriate management and genetic counseling. Since no epidemiological study has been conducted before, we have investigated frequencies, molecular and hematological features of Hb variants found in a large cohort of Thai subjects.Materials and MethodsStudy was conducted on 26,013 unrelated subjects, inhabiting in all geographical parts of Thailand over a period of 11 years from January 2002-December 2012. Hb analysis was done on high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). Mutations causing Hb variants were identified using PCR and related techniques.ResultsAmong 26,013 subjects investigated, 636 (2.4%) were found to carry Hb variants. Of these 636 subjects, 142 (22.4%) carried α-chain variants with 13 different mutations. The remaining included 451 (70.9%) cases with 16 β-chain variants, 37 (5.8%) cases with Hb Lepore (δβ-hybrid Hb) and 6 (0.9%) cases with a single δ-chain variant. The most common α-globin chain variant was the Hb Q-Thailand (α74GAC-CAC, Asp-His) which was found in 101 cases (15.8%). For β-globin chain variants, Hb Hope (β136GGT-GAT, Gly-Asp) and Hb Tak (β146+AC, Ter-Thr) are the two most common ones, found in 121 (19.0%) and 90 (14.2%) cases, respectively. Seven Hb variants have never been found in Thai population. Hb analysis profiles on HPLC or CE of these variants were illustrated to guide presumptive diagnostics.ConclusionsHb variants are common and heterogeneous in Thai population. With varieties of thalassemias and hemoglobinopathies in the population, interactions between them leading to complex syndromes are common and render their diagnoses difficult in routine practices. Knowledge of the spectrum, molecular basis, genotype-phenotype correlation and diagnostic features should prove useful for prevention and control of the diseases in the region.

Five Rare β Globin Chain Hemoglobin Variants in India

“…Hb Pyrgos is a relatively common Hb variant in the South East Asian region particularly in North East and Central Thailand. Hb Pyrgos has been co-inherited with HbH with no deleterious effect of the variant on the clinical presentation of Hb H disease [4,9]. As we identified this variant during antenatal screening for b thalassemia, the lady had no clinical presentation but the percentage of this variant was 53.4 %.…”

Elevations of Thrombotic Biomarkers in Hemoglobin H Disease

“…A total of 31 patients with Hb H disease treated at the Pediatric Clinic of the Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, from July 2014 to March 2015 were recruited. Definite diagnoses were based on Hb high-performance liquid chromatography (HPLC) and globin DNA analyses [12]. Inclusion criteria were no blood transfusion within 2 months, no medication or aspirin during the week prior to blood collection, and no antithrombotic treatment (e.g., heparin or oral anticoagulants) during the last 2 weeks.…”

Diagnosis of common hemoglobinopathies among South East Asian population using capillary isoelectric focusing system

“…Identifications of β‐thalassemia mutations, α 0 ‐thalassemia (SEA & THAI deletions) and α + ‐thalassemia (3.7 & 4.2 kb deletions), Hb Constant Spring, and Hb Paksé mutations are performed routinely in our laboratory using PCR, and related methods described elsewhere . Diagnosis of known Hb variants was made by allele‐specific PCR assays as described elsewhere . Thalassemia genotypes were defined in all cases using results obtained by Hb and DNA analyses.…”

“…In Thailand, the average frequencies are 20–30% for α‐thalassemia, 3–9% for β‐thalassemia, and up to 50% for Hb E . In addition, more than 30 different Hb variants have been documented . Interactions of these genetic variants lead to several forms of thalassemia and hemoglobinopathies which could create major public health problems in the region and difficulty in routine laboratory diagnostic.…”