Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients

Abstract

Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.

Keywords:

• β-Thalassemia intermedia (β-TI)
• genetic variants
• Hb F
• modifier loci
• single nucleotide polymorphism (SNP)

Acknowledgements

All authors sincerely thank Professor Kwong Wai Choy and Xiaofeng Wang, Ph.D., Department of Obstetrics and Gynecology, The Chinese University of Hong Kong and New Territories East Cluster, for advice and for revising this manuscript. The authors thank all the people who participated in this study.

Disclosure statement

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

Funding

This study was supported by Natural Science Foundation of China [81260093, 81660034], Natural Science Foundation of Guangxi [2013GXNSFAA019247, 2016GXNSFAA380078], the Health Department of Guangxi Province [Z2014146, Z2011060] and Guangxi Science and Technology Project [Gui 14124004–1-5, Gui 1598012–21].