Association of Genetic Variation with Gene Expression and Protein Abundance within the Natriuretic Peptide Pathway

Abstract

The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure with wide individual variability in functioning. We investigated the genetic component by testing the association of single nucleotide polymorphisms (SNP) with RNA and protein expression. Samples of DNA, RNA, and tissue from human kidney (n = 103) underwent genotyping, RT-PCR, and protein quantitation (in lysates), for four candidate genes [NP receptor 1 (NPR1), NPR2, and NPR3 and membrane metalloendopeptidase]. The association of genetic variation with expression was tested using linear regression for individual SNPs, and a principal components (PC) method for overall gene variation. Eleven SNPs in NPR2 were significantly associated with protein expression (false discovery rate ≤0.05), but not RNA quantity. RNA and protein quantity correlated poorly with each other. The PC analysis showed only NPR2 as significant. Assessment of the clinical impact of NPR2 genetic variation is needed.

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Acknowledgements

We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, USA, for the use of the Tissue Procurement Core, which provided tissue, DNA, and RNA isolation services. The Siteman Cancer Center is supported in part by a NCI Cancer Center Support Grant #P30 CA91842. This work was supported by grants from the National Institutes of Health (Lanfear, HL085124 and HL103871).

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The authors declare that they have no competing interests.

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Correspondence to David E. Lanfear.

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Associate Editor Paul J. R. Barton oversaw the review of this article

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Lanfear, D.E., Sunkara, B., Li, J. et al. Association of Genetic Variation with Gene Expression and Protein Abundance within the Natriuretic Peptide Pathway. J. of Cardiovasc. Trans. Res. 6, 826–833 (2013). https://doi.org/10.1007/s12265-013-9491-y

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Keywords

  • Natriuretic peptide
  • Heart failure
  • Gene expression
  • Pharmacogenomics
  • Nesiritide
  • Genetic polymorphisms