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 beta-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 beta-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.
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 beta-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 beta-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.
Authors: Jian Xu; Vijay G Sankaran; Min Ni; Tobias F Menne; Rishi V Puram; Woojin Kim; Stuart H Orkin Journal: Genes Dev Date: 2010-04-15 Impact factor: 11.361
Authors: John J Farrell; Richard M Sherva; Zhi-Yi Chen; Hong-Yuan Luo; Benjamin F Chu; Shau Yin Ha; Chi Kong Li; Anselm C W Lee; Rever C H Li; Chi Keung Li; Hui Leung Yuen; Jason C C So; Edmond S K Ma; Li Chong Chan; Vivian Chan; Paola Sebastiani; Lindsay A Farrer; Clinton T Baldwin; Martin H Steinberg; David H K Chui Journal: Blood Date: 2011-03-08 Impact factor: 22.113