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α ‐Haemoglobin stabilising protein is a quantitative trait gene that modifies the phenotype of β ‐thalassaemia
Author(s) -
Lai Mei I.,
Jiang Jie,
Silver Nicholas,
Best Steve,
Menzel Stephan,
Mijovic Aleksandar,
Colella Stefano,
Ragoussis Jiannis,
Garner Chad,
Weiss Mitchell J.,
Thein Swee L.
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06075.x
Subject(s) - biology , phenotype , gene expression , gene , globin , microbiology and biotechnology , alpha (finance) , genotype , genetics , reporter gene , alpha globulin , medicine , construct validity , nursing , patient satisfaction
Summary It has been suggested that altered levels or function of α ‐haemoglobin stabilising protein (AHSP), an erythroid‐specific protein that binds specifically to free α ‐(haemo)globin, might account for some of the clinical variability in β ‐thalassaemia. To assess the variation of AHSP expression, mRNA levels in circulating reticulocytes of 103 healthy individuals were measured by quantitative reverse transcription‐polymerase chain reaction. AHSP expression varied up to threefold, and did not correlate with age or sex. A systematic survey of the AHSP locus identified eight sequence variants, of which six were common. Four common variants, including the longer homopolymer (T18) in the putative promoter, are strongly associated with AHSP expression. Reporter assays in K562 cells showed that the activity of the shorter (T15) reporter was relatively lower than that of the T18 reporter. In a study of nine anaemic patients who were heterozygous for β ‐thalassaemia and also heterozygous for the triplicated α ‐globin gene ( α α α / α α ), frequency of the shorter homopolymer was higher than expected. AHSP expression is variable, with cis control accounting for some of its variance. In some families, the subtle altered levels in AHSP related to the AHSP genotype appears to be a relevant contributory factor in the haematological phenotype.