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Genetic polymorphisms of vitamin D receptor (VDR) in Fabry disease

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Abstract

Fabry disease, an X-linked inborn error of metabolism, is characterized by multi-organ involvement including cardiac signs of left ventricular hypertrophy and abnormal intima-medial (IMT) thickening of arteries, progressive renal failure, neurological involvement, and more. The vitamin D receptor (VDR) and an enzyme producing vitamin D3 result in an autocrine loop with direct effects on blood vessels. The purpose of this study is to assess VDR polymorphisms (BsmI, FokI, ApaI, and TaqI) relative to clinically important disease parameters using a disease-specific severity score (MSSI) and haplotype analysis. There were statistically significant differences between females (43% of 74 patients) and males in MSSI total scores, and in general and neurologic sub-scores. There appears to be a protective effect of the TaqI tt genotype so that there were significantly lower scores in clinical categories between those with the tt genotype versus those with the TT genotype. Multivariate models of haplotypes with MSSI scores reveal that T-A-f-B and t-a-F-b haplotypes of the VDR gene polymorphisms are significantly associated with variation in the Fabry phenotype. Despite the limitations of using the MSSI score as a clinical correlate, these results are provocative and further studies in larger cohorts with more males are recommended.

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Acknowledgments

The authors would like to acknowledge the dedication and assistance provided by Sandra Delgado Sanchez, the Study nurse.

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Authors and Affiliations

  1. Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel

    Michael Teitcher, Sarah Weinerman & Deborah Elstein

  2. Children’s Hospital, University of Mainz, Mainz, Germany

    Catharina Whybra & Michael Beck

  3. Department of Statistics, School of Public Health, Hebrew University, Jerusalem, Israel

    Nir Sharon

  4. Genetic Unit, Shaare Zedek Medical Center, Jerusalem, Israel

    Gheona Altarescu

Authors
  1. Michael Teitcher
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  2. Sarah Weinerman
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  3. Catharina Whybra
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  4. Michael Beck
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  5. Nir Sharon
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  6. Deborah Elstein
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  7. Gheona Altarescu
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Corresponding author

Correspondence to Deborah Elstein.

Additional information

Mr. Teitcher and Ms. Weinerman contributed equally to this study.

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Teitcher, M., Weinerman, S., Whybra, C. et al. Genetic polymorphisms of vitamin D receptor (VDR) in Fabry disease. Genetica 134, 377–383 (2008). https://doi.org/10.1007/s10709-008-9245-y

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  • DOI: https://doi.org/10.1007/s10709-008-9245-y

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