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Influence of single nucleotide polymorphisms in the BCL11A, HBS1L-MYB intergenic region, and HBB gene cluster on the fetal hemoglobin levels in Bangladeshi patients with Beta-thalassemia/hemoglobin E disease |
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| รหัสดีโอไอ | |
| Creator | Jenjira Chalerm |
| Title | Influence of single nucleotide polymorphisms in the BCL11A, HBS1L-MYB intergenic region, and HBB gene cluster on the fetal hemoglobin levels in Bangladeshi patients with Beta-thalassemia/hemoglobin E disease |
| Contributor | Jenjira Chalerm, Mahmood Ahmed Chowdhury, Chayanon Peerapittayamongkol, Kittiphong Paiboonsukwong, Suthat Fucharoen, Orapan Sripichai |
| Publisher | Genetics Society of Thailand |
| Publication Year | 2560 |
| Journal Title | Genomics and Genetics |
| Journal Vol. | 10 |
| Journal No. | 1&2 |
| Page no. | 21-26 |
| Keyword | ?-thalassemia, HbE, fetal hemoglobin, HbF, SNPs |
| URL Website | https://www.tci-thaijo.org/index.php/gst/issue/view/7723 |
| Website title | https://www.tci-thaijo.org/index.php/gst/article/view/86053 |
| ISSN | 24655198 |
| Abstract | Thalassemia is considered a major health burden in the Southeast Asian and Indian populations. Patients with ?-thalassemia display disease heterogeneity ranging from nearly asymptomatic to severe anemia with complications. Increased levels of fetal hemoglobin (HbF) can ameliorate the clinical severity of ?-thalassemia patients. The HbF production is influenced by many quantitative trait loci (QTL). Three major HbF-QTLs are the BCL11A gene, the HBS1L-MYB intergenic region (HMIR), and the ?-globin (HBB) gene cluster. Therefore, this study aimed to evaluate the influence of these genetic modifiers (BCL11A, rs766432; HMIR, rs4895411; and HBB cluster, rs2071348) on the HbF levels in Bangladeshi patients with ?-thalassemia/HbE disease. The cohort study comprised of 90 patients with ?-thalassemia/HbE disease from in and around the area of Chittagong, Southeast Bangladesh. The HbF levels ranged from 7.9% to 59.1%. The results showed that levels of HbF were primarily influenced by alleles of the HBB cluster (rs2071348), and to a lesser extent by rs766432 HBL11A gene and HMIP (rs4895441) loci. The rs2071348 SNP explained 12.5% of the variation in the HbF levels, while 3.6% and 3.9% of trait variation were explained by rs766432 and rs4895441, respectively. In a case-control model of the low and high HbF analysis, we found that genotypes AC and AA (p = 2.0?10-4) and the allele C (p = 2.0?10-4) of rs2071348, and genotypes AG and GG (p = 0.02) and the allele G (p = 0.05) of rs4895441were associated with a significantly higher frequency with high HbF. However, the rs766432 did not exhibit such features. Our results suggest these three major HbF-QTLs as the influencing phenotypic factors of ?-thalassemia in Bangladeshi ?-thalassemia/HbE patients. |
