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Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter

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Abstract

Methylation of CpG sites in the promoter region can affect gene transcription. DNA derived from peripheral blood leukocytes (PBL) from the well-characterized clinical cohorts might be useful to study the influence of environmental factors on DNA methylation. However, these studies could be confounded by the heterogeneous nature of PBL. The aims of this study were to determine the impact of PBL distribution on methylation status of the androgen receptor (AR) promoter, and determine the associations between PBL distribution-adjusted methylation status of the AR promoter and AR-related phenotypes. PBL differential count analyses were performed at the time of blood sampling for DNA preparation in 170 elderly men. The DNA was bisulfite treated, and the methylation status of five CpG units in the AR promoter was analyzed using a high-throughput technique based on MALDI-TOF mass spectrometry. The degree of methylation of all the five investigated CpG units was strongly positively associated with the percent of lymphocytes in the PBL (r s = 0.17–0.49, P < 0.05). Furthermore, the PBL distribution-adjusted methylation status of a specific CpG unit in the AR promoter was significantly associated with body mass index (r s = 0.24) and other measures reflecting fat mass in elderly men. In conclusion, adjustment for PBL distribution needs to be done to be able to use DNA from whole blood for methylation analysis of the AR promoter and most likely also when investigating other promoters.

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Acknowledgments

This study was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, The ALF/LUA research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Söderberg’s Foundation, Petrus and Augusta Hedlunds Foundation, the Novo Nordisk Foundation, the Magnus Bergvall Foundation, and the Tore Nilson Foundation.

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Authors and Affiliations

  1. Division of Endocrinology, Departments of Internal Medicine and Geriatrics, Center for Bone Research at the Sahlgrenska Academy (CBS), University of Gothenburg, Gröna Stråket 8, 413 45, Gothenburg, Sweden

    Sofia Movérare-Skrtic, Dan Mellström, Liesbeth Vandenput & Claes Ohlsson

  2. SEQUENOM Inc., San Diego, CA, USA

    Mathias Ehrich

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  1. Sofia Movérare-Skrtic
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  2. Dan Mellström
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  3. Liesbeth Vandenput
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  5. Claes Ohlsson
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Correspondence to Sofia Movérare-Skrtic.

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Movérare-Skrtic, S., Mellström, D., Vandenput, L. et al. Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter. Endocr 35, 204–210 (2009). https://doi.org/10.1007/s12020-009-9153-7

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  • DOI: https://doi.org/10.1007/s12020-009-9153-7

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