HbA2 levels in normal adults are influenced by two distinct genetic mechanisms
作者： Stephan Menzel , Chad Garner , Helen Rooks , Tim D. Spector , Swee Lay Thein
DOI: 10.1111/BJH.12084
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摘要: Using a genome-wide association study, we found that common inter-individual differences in haemoglobin A(2) (HbA(2) , α(2) δ(2) ) levels are largely governed by genetic factors (42% of variability). The influence age (1%) and sex (4%) was small. HbA(2) were influenced two loci: the HBS1L-MYB locus on chromosome 6q, which has been shown to have pleiotropic effects other haematological traits; second surrounding HBB, gene encoding β-globin. Our results suggest adults different biological processes: one via kinetics erythropoiesis, other, competition between HBB HBD activity.
sci-hub.se 参考文章(16)
D. J. Weatherall, J. B. Clegg, The thalassaemia syndromes ,(1972)
Urszula Wojda, Pierre Noel, Jeffery L. Miller, Fetal and adult hemoglobin production during adult erythropoiesis: coordinate expression correlates with cell proliferation Blood. ,vol. 99, pp. 3005- 3013 ,(2002) , 10.1182/BLOOD.V99.8.3005
Robert‐Jan Palstra, Wouter de Laat, Frank Grosveld, Chapter 4 β‐Globin Regulation and Long‐Range Interactions Advances in Genetics. ,vol. 61, pp. 107- 142 ,(2008) , 10.1016/S0065-2660(07)00004-1
JF Codrington, HW Li, F Kutlar, LH Gu, M Ramachandran, TH Huisman, Observations on the levels of Hb A2 in patients with different beta- thalassemia mutations and a delta chain variant Blood. ,vol. 76, pp. 1246- 1249 ,(1990) , 10.1182/BLOOD.V76.6.1246.BLOODJOURNAL7661246
Bernard G. Forget, Ross C. Hardison, Martin H. Steinberg, Bernard G. Forget, Douglas R. Higgs, David J. Weatherall, The Normal Structure and Regulation of Human Globin Gene Clusters Cambridge University Press. pp. 46- 61 ,(2009) , 10.1017/CBO9780511596582.007
S. L. Thein, S. Menzel, X. Peng, S. Best, J. Jiang, J. Close, N. Silver, A. Gerovasilli, C. Ping, M. Yamaguchi, K. Wahlberg, P. Ulug, T. D. Spector, C. Garner, F. Matsuda, M. Farrall, M. Lathrop, Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 11346- 11351 ,(2007) , 10.1073/PNAS.0611393104
Lucia Perseu, Stefania Satta, Paolo Moi, Franca Rosa Demartis, Laura Manunza, Maria Carla Sollaino, Susanna Barella, Antonio Cao, Renzo Galanello, KLF1 gene mutations cause borderline HbA(2). Blood. ,vol. 118, pp. 4454- 4458 ,(2011) , 10.1182/BLOOD-2011-04-345736
Stephan Menzel, Chad Garner, Ivo Gut, Fumihiko Matsuda, Masao Yamaguchi, Simon Heath, Mario Foglio, Diana Zelenika, Anne Boland, Helen Rooks, Steve Best, Tim D Spector, Martin Farrall, Mark Lathrop, Swee Lay Thein, None, A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nature Genetics. ,vol. 39, pp. 1197- 1199 ,(2007) , 10.1038/NG2108
Stephan Menzel, Jie Jiang, Nicholas Silver, Joy Gallagher, Juliette Cunningham, Gabriela Surdulescu, Mark Lathrop, Martin Farrall, Tim D. Spector, Swee Lay Thein, The HBS1L-MYB intergenic region on chromosome 6q23.3 influences erythrocyte, platelet, and monocyte counts in humans Blood. ,vol. 110, pp. 3624- 3626 ,(2007) , 10.1182/BLOOD-2007-05-093419
T.H.J. Huisman, Levels of Hb A2 in heterozygotes and homozygotes for beta-thalassemia mutations: influence of mutations in the CACCC and ATAAA motifs of the beta-globin gene promoter. Acta Haematologica. ,vol. 98, pp. 187- 194 ,(1997) , 10.1159/000203622