Fine mapping of quantitative trait nucleotides underlying thrombin-activatable fibrinolysis inhibitor antigen levels by a transethnic study

被引:36
作者
Frere, Corinne
Tregouet, David-Alexandre
Morange, Pierre-Emmanuel
Saut, Noemie
Kouassi, Dinar
Juhan-Vague, Irene
Tiret, Laurence
Alessi, Marie-Christine [1 ]
机构
[1] INSERM, UMR 626, F-13385 Marseille, France
[2] CHU Timone, Fac Med, Marseille, France
[3] INSERM, Inst Fed Rech 14, U525, Paris, France
[4] Univ Paris 06, Paris, France
关键词
D O I
10.1182/blood-2006-01-008094
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies revisiting the association between plasma thrombin-activatable fibrinolysis inhibitor (TAFI) Ag levels and polymorphisms of the CPB2gene (coding for TAFI) suggested that TAFI Ag levels were influenced by 2 major quantitative trait nucleotides (QTNs) in European whites. However, the strong linkage disequilibrium (LD) between CPB2 polymorphisms in European whites did not allow one to distinguish which polymorphisms could be the putative QTNs. To get a better insight into the identification of QTNs, a transethnic haplotype analysis contrasting 2 populations of African and European subjects was performed using 13 CPB2 polymorphisms. Results of the haplotype analyses suggested that 3 QTNs had independent effects and explained about 15% of the TAFI variability, consistently in the 2 populations. The lower LD observed in the African population enabled us to identify the 1583T > A SNP located in 3'UTR as one of these QTNs, whereas the -2599C > G and -2345--2344insG SNPs located in the 5' region might be the 2 other QTNs. A phylogenetic study suggested that these 3 polymorphisms occurred before the period of migration "out of Africa." Although this transethnic comparison contributed to better map the putative CPB2 QTNs, further studies are required to clarify the role of the promoter region.
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收藏
页码:1562 / 1568
页数:7
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