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Genetic and environmental factors influencing the human factor H plasma levels

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Abstract

Factor H is a plasma protein that plays a critical role in the regulation of complement activation in fluid phase and on cellular surfaces. Over the years numerous reports have illustrated the association of factor H deficiencies with chronic renal and infectious diseases. Plasma levels of factor H show a five-fold range of variation in humans (116–562 μg/ml), which may also be relevant to disease susceptibility. To quantify the effects of the genetic and environmental factors responsible for the variation in the factor H plasma levels, we have applied variance-component methods to a family-based sample. Factor H plasma levels show an age-dependent increase (P<0.0001) and are decreased in smokers (P<0.0001). Interestingly, the heritability of the factor H trait is very high (h 2=0.62±0.07; P<0.0001), indicating that 62% of the factor H phenotypic variance is due to the additive effects of genes. On this premise, we conducted a genome-wide linkage screen in order to identify genes regulating the factor H trait. Three genomic regions (1q32, 2p21–24 and 15q22–24) provided suggestive evidence of linkage (LOD scores 2.03, 2.15 and 2.00, respectively) with the plasma levels of factor H.

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Acknowledgements

This study was supported by grants NIH USA HL70751, FIS 02/0375 from the Fondo Investigación Sanitaria, SAF2002/03449 and SAF2002/01083 from the Spanish Ministry of Science and Technology, 08.6/0028.1/2000 from the Comunidad de Madrid, Fundació “La Caixa” and Fundació de Investgació Sant Pau. Dr. J.M. Soria was supported by the FIS 99/3048 grant from the Fondo de Investigación Sanitaria. J. Esparza-Gordillo was supported by a grant from the Comunidad Autónoma de Madrid. A. Buil was supported by the FIS 01/A046 grant from the Fondo Investigación Sanitaria. We are deeply grateful to the families that participated in this study.

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Authors and Affiliations

  1. Departamento de Inmunología, Laboratorio 143, Centro de Investigaciones Biológicas (CSIC), C/ Ramiro de Maeztu Nº 9, 28040 , Madrid, Spain

    Jorge Esparza-Gordillo & Santiago Rodríguez de Córdoba

  2. Departamento de Hematología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    José Manuel Soria, Alfonso Buil & Jordi Fontcuberta

  3. Department of Population Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA

    Laura Almasy & John Blangero

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  1. Jorge Esparza-Gordillo
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  2. José Manuel Soria
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  3. Alfonso Buil
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  4. Laura Almasy
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  6. Jordi Fontcuberta
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  7. Santiago Rodríguez de Córdoba
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Correspondence to Santiago Rodríguez de Córdoba.

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Esparza-Gordillo, J., Soria, J.M., Buil, A. et al. Genetic and environmental factors influencing the human factor H plasma levels. Immunogenetics 56, 77–82 (2004). https://doi.org/10.1007/s00251-004-0660-7

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  • DOI: https://doi.org/10.1007/s00251-004-0660-7

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