Molecular epidemiology and hematological profiles of hemoglobin variants in southern Thailand.

Data on hemoglobin (Hb) variants in southern Thailand are lacking. This study aimed to reassess the frequency of Hb variants and the clinical aspects of compound heterozygous Hb variant with other hemoglobinopathies. We enrolled 13,391 participants from ten provinces in southern Thailand during 2015-2022. Hb analysis was performed using capillary electrophoresis, and mutations in the HBA and HBB genes were identified using PCR or DNA sequencing. Hb variants were identified in 337 (2.5%) unrelated subjects. Nine ß-chain variants, namely Hb Malay (76.9%), Hb C (10.1%), Hb D-Punjab (2.9%), Hb G-Makassar (2.3%), Hb Dhonburi (2.3%), Hb Tak (1.4%), Hb J-Bangkok (1.4%), Hb New York (0.3%), and Hb Hope (0.3%), and four α-chain variants-Hb G-Georgia (HBA1) (0.9%), Hb G-Georgia (HBA2) (0.3%), Hb Q-Thailand (0.6%), and Hb St. Luke's-Thailand (0.3%)-were identified. The southern population exhibited a distinct spectrum of Hb variants compared to that observed in the populations from other areas. Several compound heterozygous genotypes were also identified. Combining Hb Malay with Hb E or high Hb F determinants did not require a blood transfusion. This study provides essential information for genetic counseling in thalassemia prevention and control programs in this region.

Genetics background of ß-thalassemia (3.5 kb deletion) in Southern Thailand: Haplotype analysis using novel reverse dot blot hybridization.

ß-thalassemia (ß-thal) (3.5 kb deletion or NC_000011.10:g.5224302-5227791del3490bp) is a common mutation in southern Thailand. This study aimed to determine genetic diversity in subjects with ß-thal (3.5 kb deletion) alleles and to ascertain the origin of this mutation using haplotype and phylogenetic analysis. The study was carried out on members of the southern Thai population, including 45 normal individuals, 116 heterozygous ß-thal (3.5 kb deletion) and one homozygous ß-thal (3.5 kb deletion). The 5'-haplotype in ß-globin gene cluster was examined using newly developed reverse dot blot hybridization (RDB) and compared with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed 100% concordance between the haplotype patterns of these two methods. From a total of 324 chromosomes, nine haplotypes were segregated. Haplotype H2 (+ - - - -) was the predominant haplotype observed in all 118 ß-thal (3.5 kb deletion) chromosomes, which revealed a single origin. The phylogenetic tree demonstrated that ß-thal (3.5 kb deletion) has an older genetic defect in this region. Moreover, the developed RDB is simple, less time-consuming, inexpensive, and does not restriction enzyme digestion.

Association Between Genetic Polymorphisms and Hb F Levels in Heterozygous ß-Thalassemia 3.5 kb Deletions.

Single nucleotide polymorphisms (SNPs) in several genetic modifying factors have been related to Hb F levels, including Gγ XmnI polymorphism, B-cell lymphoma/leukemia 11 A (BCL11A), HBS1L-MYB intergenic polymorphism (HMIP) and a mutation in the Krüppel-like factor 1 (KLF1). This study aimed to determine whether genetic variability of these modifying factors affects Hb F levels in heterozygous ß-thalassemia (ß-thal) 3.5 kb deletion (NC_000011.10: g.5224302-5227791del13490bp). A total of 111 ß-thal 3.5 kb deletion carriers with Hb F levels ranging from 0.9 to 18.4% was recruited for this study. Genotyping of SNPs including HBG2 rs7482144, HMIP rs4895441 and rs9399137, BCL11A rs4671393 and KLF1 rs2072596 was identified. Multiple regression analyses showed that only two SNPs (HMIP rs4895441 and rs9399137) influenced Hb F levels. Interestingly, a combination of these two SNPs was associated with higher Hb F levels. Our study is the first to demonstrate that the rs4895441, rs9399137 of HMIP are associated with elevated Hb F levels in the heterozygous ß-thal 3.5 kb deletion.