A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function

被引：97

作者：

Soranzo, Nicole ^{[3
,4
]}

Rendon, Augusto ^{[1
,2
]}

Gieger, Christian ^{[5
]}

Jones, Chris I. ^{[6
]}

Watkins, Nicholas A. ^{[1
,2
]}

Menzel, Stephan

Doering, Angela ^{[5
]}

Stephens, Jonathan ^{[1
,2
]}

Prokisch, Holger ^{[7
,8
]}

Erber, Wendy ^{[1
,2
,9
]}

Potter, Simon C. ^{[3
]}

Bray, Sarah L. ^{[10
]}

Burns, Philippa ^{[1
,2
]}

Jolley, Jennifer ^{[1
,2
]}

Falchi, Mario ^{[4
,11
]}

Kuehnel, Brigitte ^{[5
]}

Erdmann, Jeanette ^{[12
]}

Schunkert, Heribert ^{[12
]}

Samani, Nilesh J. ^{[13
]}

Illig, Thomas ^{[5
]}

Garner, Stephen F. ^{[1
,2
]}

Rankin, Angela ^{[1
,2
]}

Meisinger, Christa ^{[5
]}

Bradley, John R. ^{[14
]}

Thein, Swee Lay

Goodall, Alison H. ^{[13
]}

Spector, Tim D. ^{[4
]}

Deloukas, Panos ^{[3
]}

Ouwehand, Willem H. ^{[1
,2
,3
]}

机构：

[1] Univ Cambridge, Dept Haematol, Cambridge CB2 2PT, England

[2] NHS Blood & Transplant, Cambridge, England

[3] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England

[4] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[5] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[6] Univ Reading, Sch Biol Sci, Reading, Berks, England

[7] Tech Univ Munich, Inst Human Genet, Munich, Germany

[8] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[9] Cambridge Univ Hosp NHS Fdn Trust, Dept Haematol, Cambridge, England

[10] Univ Forvie Site, Biostat Unit, MRC, Cambridge, England

[11] Univ London Imperial Coll Sci Technol & Med, London, England

[12] Univ Lubeck, Med Klin 2, Lubeck, Germany

[13] Univ Leicester, Leicester, Leics, England

[14] Univ Cambridge, Sch Clin Med, Dept Med, Cambridge CB2 1TN, England

来源：

BLOOD | 2009年 / 113卷 / 16期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; DEPENDENT PROTEIN-KINASE; BLOOD CELL COUNTS; PROPLATELET FORMATION; TRANSCRIPTION FACTOR; DIFFERENTIATED MEGAKARYOCYTES; GENE; MICROARRAY; DISORDERS; LOCI;

D O I：

10.1182/blood-2008-10-184234

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 +/- 0.001 log fL; P < 1.08 x 10(-24)) and PLT (per-G effect -4.55 +/- 0.80 10(9)/L; P < 7.19 x 10(-8)) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis. (Blood. 2009; 113: 3831-3837)

引用

页码：3831 / 3837

页数：7

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