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Genomewide linkage analysis of soluble transferrin receptor plasma levels

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Abstract

Genetic control of soluble transferrin receptor (sTfR) levels was demonstrated using family-based studies (GAIT, Genetic Analysis of Idiopathic Thrombophilia project); moreover, a genetic relationship was observed between sTfR and the risk for thrombosis, suggesting that these phenotypes shared genetic determinants. We studied the regions that control sTfR. To assess such regions, a full genome scan was carried out using 604 highly polymorphic deoxyribonucleic acid markers (resolution 7.3 cM) in 21 extended pedigrees (358 individuals). Then, a quantitative trait linkage analysis was performed using variance components methods. The genomewide scan linkage analysis showed two regions (quantitative trait locus or QTL) with significant limit of detection (LOD) scores (2q23.14, LOD score=2.64, nominal p=0.00024; 3q21.2, LOD score=1.94, nominal p=0.0014). There were no obvious candidate genes in these regions. In conclusion, this linkage analysis suggested the existence of a QTL in 2q23.14 that probably harbored a gene (or genes) controlling sTfR levels. Moreover, a second linkage signal was observed in 3q21.2; albeit the evidence for this second locus was lower. The next step will be to identify the gene(s) and its possible involvement in thrombosis and iron homeostasis.

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Acknowledgements

We are grateful to the Ministerio de Sanidad y Consumo (Spain) (grant FIS PI 20506), Fundació “la Caixa,” and Fundació d’Investigació Sant Pau for supporting this study. J. M. Soria and A. Buil were supported by FIS 99/3048 and FIS 01/A046, respectively. Statistical genetic analysis was supported by US National Institutes of Health grants MH59490 and HL70751.

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Authors and Affiliations

  1. Hematology Department, Hospital de Sant Pau, Avda Padre Claret 167, Barcelona, 08025, Spain

    Angel F. Remacha, Joan C. Souto, José Manuel Soria, Alfonso Buil, M. Pilar Sardà & Jordi Fontcuberta

  2. Centre National de Genotypage, Evry, France

    Mark Lathrop

  3. Southwest Foundation for Biomedical Research, San Antonio, TX, USA

    John Blangero & Laura Almasy

Authors
  1. Angel F. Remacha
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  2. Joan C. Souto
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  3. José Manuel Soria
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  4. Alfonso Buil
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  5. M. Pilar Sardà
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  6. Mark Lathrop
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  7. John Blangero
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  8. Laura Almasy
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  9. Jordi Fontcuberta
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Correspondence to Angel F. Remacha.

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Remacha, A.F., Souto, J.C., Soria, J.M. et al. Genomewide linkage analysis of soluble transferrin receptor plasma levels. Ann Hematol 85, 25–28 (2006). https://doi.org/10.1007/s00277-005-1092-7

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  • DOI: https://doi.org/10.1007/s00277-005-1092-7

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