LETTERS TO JMG

The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of β-thalassaemia

C-C So¹, Y-Q Song², S T Tsang¹, L-F Tang², A Y Chan¹, E S Ma³, L-C Chan¹

¹ Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
² Department of Biochemistry, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
³ Department of Pathology, Hong Kong Sanatorium and Hospital, Hong Kong SAR, China

Dr C-C So, Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; scc{at}pathology.hku.hk

Background: Fetal haemoglobin (HbF) level modifies the clinical severity of HBB disorders. Intergenic variants of HBS1L-MYB on chromosome 6q23 have recently been shown to be a major quantitative trait locus (QTL) influencing HbF levels in normal Caucasian adults.

Methods: A unique and well-characterised cohort of 238 Chinese subjects with β-thalassaemia trait was used to conduct a single-nucleotide polymorphism (SNP) association study for HbF level.

Results: Within this locus, 29 trait-associated SNPs in a non-coding 56 kb segment were identified. They were divided into five linkage disequilibrium (LD) blocks in the Chinese participants.

Conclusions: The data independently validate for the first time the significance of the HBS1L-MYB intergenic region in regulating HbF expression in a separate ethnic group that has a high prevalence of β-thalassaemia. Functional studies to unravel the biological significance of this region in regulating HbF production is clearly indicated, which may lead to new strategies to modify the disease course of severe HBB disorders.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Thein, S. L., Menzel, S., Lathrop, M., Garner, C. (2009). Control of fetal hemoglobin: new insights emerging from genomics and clinical implications. Hum Mol Genet 18: R216-R223 [Abstract] [Full Text]  
• Wahlberg, K., Jiang, J., Rooks, H., Jawaid, K., Matsuda, F., Yamaguchi, M., Lathrop, M., Thein, S. L., Best, S. (2009). The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells. Blood 114: 1254-1262 [Abstract] [Full Text]