Genotyping of BCL11A and HBS1L-MYB Single Nucleotide Polymorphisms in β-thalassemia/HbE and Homozygous HbE Subjects with Low and High Levels of HbF

Abstract

Whether multiple single nucleotide polymorphisms (SNPs) of BCL11A and HBS1L-MYB genes affect hemoglobin (Hb)F production and hematological parameter variation in β-thalassemia/HbE and homozygous HbE in Thai subjects with low and high HbF levels are still unclear. Three SNPs of BCL11A gene (rs1427407, rs10189857 and rs11886868) and 3 SNPs of HBS1L-MYB gene (rs4895441, rs9399137 and rs28384513) were analyzed in 45 β-thalassemia/HbE patients who had HbF levels lower and higher than 15 %, and in 50 homozygous HbE who had HbF levels lower and higher than 5 %. Their hematological parameters were measured using automated blood counter. The HbF level was analyzed using high performance liquid chromatography (HPLC). There were no statistical significant differences of allele and genotype frequencies of 3 SNPs in the BCL11A gene between the groups of β-thalassemia/HbE patients and homozygous HbE subjects with low and high HbF levels. Significant differences in the allele frequencies in HBS1L-MYB SNP rs4895441 (p = 0.041) and rs9399137 (p = 0.048) were observed in homozygous HbE subjects with HbF £ 5 % and > 5 %. Moreover, significant differences in MCV (p = 0.005) and trends towards significant differences in MCH (p = 0.057) and HbF levels (p = 0.051) were found in HBS1L-MYB SNP rs9399137 of homozygous HbE subjects. Therefore, the HBS11L-MYB SNPs especially rs9399137 had an effect on HbF production and the variation of hematological parameters in homozygous HbE subjects, but not in β-thalassemia/HbE patients.

Single Nucleotide Polymorphisms in XMN1-HBG2, HBS1L-MYB, and BCL11A and Their Relation to High Fetal Hemoglobin Levels That Alleviate Anemia

“…The HbF level among SCD in patients of European descent is similar to the range in Thai patients [ 51 , 59 ]. The SNPs of rs48954419 (A-G), rs9399137 (T-C), and rs28384513 (A-C) have a high possibility of ameliorating severe anemia and hemoglobinopathies, especially with SNP rs9399137, due to significantly different MCV ( p < 0.05), MCH ( p < 0.05), and HbF levels ( p < 0.05) [ 51 ]. Another study in a cohort from Sabah showed that rs9399137 (T-C) and rs11759553 (A-T) SNPs were frequently present in β 0 -thalassemia patients of Filipino descent ( n = 34, MAF = 0.15 and 0.18); these patients have mean HbF values between 1.7% and 3.4% [ 63 ].…”

“…SNPs rs4895441 (A-G), rs9399137 (T-C), and rs28384513 (A-C) are related, with 3.8% to 32% of HbF level variation in HBS1L-MYB among β-thalassemia/HbE and homozygous HbE in the Thai population [ 51 ]. The HbF level among SCD in patients of European descent is similar to the range in Thai patients [ 51 , 59 ].…”

“…SNPs rs4895441 (A-G), rs9399137 (T-C), and rs28384513 (A-C) are related, with 3.8% to 32% of HbF level variation in HBS1L-MYB among β-thalassemia/HbE and homozygous HbE in the Thai population [ 51 ]. The HbF level among SCD in patients of European descent is similar to the range in Thai patients [ 51 , 59 ]. The SNPs of rs48954419 (A-G), rs9399137 (T-C), and rs28384513 (A-C) have a high possibility of ameliorating severe anemia and hemoglobinopathies, especially with SNP rs9399137, due to significantly different MCV ( p < 0.05), MCH ( p < 0.05), and HbF levels ( p < 0.05) [ 51 ].…”

Epigenetic Insights and Potential Modifiers as Therapeutic Targets in β–Thalassemia

“…In an Indonesian cohort, the minor allele of BCL11A SNP rs11886868 was associated with increased HbF concentration in HbE/ β –thalassemia patients (n = 118), while the minor allele of rs766432 was associated with an even greater increase in HbF (4.7% more) [ 32 ]. In contrast, in a Thai cohort, there was no association between three BCL11A SNPs (rs1427407, rs10189857, and rs11886868) and HbF levels in HbE/ β –thalassemia (n = 45) and homozygous HbE (n = 50) patients [ 33 ]. In severe (n = 383) and mild (n = 235) HbE/β 0 -thalassemia in Thai and Thai–Chinese patients, rs766432 was significantly associated with disease severity ( p = 5.87 × 10 −10 ) and HbF level ( p = 1.00 × 10 −7 ).…”

“…In addition, in homozygous HbE subjects, rs9399137 was significantly associated with differences in mean corpuscular volume (MCV; p = 0.005) and trended toward significant associations with mean corpuscular hemoglobin (MCH) ( p = 0.057) and HbF levels ( p = 0.051). These results suggest that rs9399137 plays a role in the variation of HbF production and hematological parameters, specifically in homozygous HbE subjects, but not in HbE/ β –thalassemia patients [ 33 ]. Another HBS1L-MYB SNP, rs9376092, was significantly associated with disease severity ( p = 2.36 × 10 −10 ) in severe (n = 383) and mild (n = 235) HbE/β 0 -thalassemia cases in Thai and Thai–Chinese patients.…”