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

Abstract

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 β-thalassemia (β-thal) 3.5 kb deletion (NC_000011.10: g.5224302-5227791del13490bp). A total of 111 β-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 β-thal 3.5 kb deletion.

Keywords:

• BCL11A
• Hb F
• HBS1L-MYB
• Krüppel-like factor 1 (KLF1)
• XmnI polymorphism

Acknowledgments

The authors thank Mr. Dave Patterson of the International Affairs Office, Faculty of Medicine, Prince of Songkla University for editing the manuscript. W. Tepakhan was responsible for acquisition of the grant, designed the study, performed the experiments, analyzed the data and drafted the manuscript. S. Kanjanaopas and K. Srewaradachpisal performed the experiments. All authors read and approved the final submitted manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by a grant from the Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand [REC 60-170-05-2].