Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier in patients with β thalassemia

被引:82
作者
Viprakasit, V [1 ]
Tanphaichitr, VS
Chinchang, W
Sangkla, P
Weiss, MJ
Higgs, DR
机构
[1] Mahidol Univ, Dept Pediat, Bangkok 10700, Thailand
[2] Mahidol Univ, Siriraj Hosp, Fac Med, Siriraj Thalassemia Res Program, Bangkok 10700, Thailand
[3] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DU, England
[4] Surin Gen Hosp, Dept Pediat, Surin, Thailand
[5] Univ Penn, Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA
关键词
D O I
10.1182/blood-2003-11-3957
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although beta thalassemia is considered to be a classic monogenic disease, it is clear that there is considerable clinical variability between patients who inherit identical beta globin gene mutations, suggesting that there may be a variety of genetic determinants influencing different clinical phenotypes. It has been suggested that variations in the structure or amounts of a highly expressed red cell protein (alpha hemoglobin stabilizing protein (AHSP]), which can stabilize free a globin chains in vitro, could influence disease severity in patients with beta thalassemia. To address this hypothesis, we studied 120 patients with Hb E-beta thalassemia with mild, moderate, or severe clinical phenotypes. Using gene mapping, direct genomic sequencing, and extended haplotype analysis, we found no mutation or specific association between haplotypes of AHSP and disease severity in these patients, suggesting that AHSP is not a disease modifier in Hb E-beta thalassemia. It remains to be seen if any association between AHSP and clinical severity is present in other population groups with a high frequency of beta thalassemia. (C) 2004 by The American Society of Hematology.
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收藏
页码:3296 / 3299
页数:4
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