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

作者：Soranzo Nicole; Rendon Augusto; Gieger Christian; Jones Chris I; Watkins Nicholas A; Menzel Stephan; Doering Angela; Stephens Jonathan; Prokisch Holger; Erber Wendy; Potter Simon C; Bray Sarah L; Burns Philippa; Jolley Jennifer; Falchi Mario; Kuehnel Brigitte; Erdmann Jeanette; Schunkert Heribert; Samani Nilesh J; Illig Thomas; Garner Stephen F; Rankin Angela; Meisinger Christa; Bradley John R; Thein Swee Lay; Goodall Alison H; Spector Tim D; Deloukas Panos

来源：Blood, 2009, 113(16): 3831-3837.

DOI：10.1182/blood-2008-10-184234

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)

• 出版日期2009-4-16