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A polymorphism in HLA-G modifies statin benefit in asthma

The Pharmacogenomics Journal volume 15, pages 272–277 (2015)Cite this article

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Abstract

Several reports have shown that statin treatment benefits patients with asthma; however, inconsistent effects have been observed. The mir-152 family (148a, 148b and 152) has been implicated in asthma. These microRNAs suppress HLA-G expression, and rs1063320, a common SNP in the HLA-G 3′UTR that is associated with asthma risk, modulates miRNA binding. We report that statins upregulate mir-148b and 152, and affect HLA-G expression in an rs1063320-dependent fashion. In addition, we found that individuals who carried the G minor allele of rs1063320 had reduced asthma-related exacerbations (emergency department visits, hospitalizations or oral steroid use) compared with non-carriers (P=0.03) in statin users ascertained in the Personalized Medicine Research Project at the Marshfield Clinic (n=421). These findings support the hypothesis that rs1063320 modifies the effect of statin benefit in asthma, and thus may contribute to variation in statin efficacy for the management of this disease.

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Acknowledgements

The work was supported by NIH grants U19 HL069757, R01 HL104133, UL1TR000427, U01 HG006389, U19 HL065962, U01 HL065899 and K08 HL088046. The PGPop Consortium was initiated and funded as a PGRN Network Resource through the grant NIH U19 HL065962 awarded to Vanderbilt University. Additional consortium members include Marshfield Clinic, Kaiser Permanente GA, Kaiser Permanente Hawaii, Harvard Pilgrim, Brigham & Women’s Hospital and RIKEN Center for Integrative Medical Sciences.

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Authors and Affiliations

  1. Atherosclerosis Research, Children’s Hospital Oakland Research Institute, Oakland, CA, USA

    D Naidoo & M W Medina

  2. Department of Population Medicine, Harvard Medical School, Boston, MA, USA,

    A C Wu

  3. Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA

    M H Brilliant & T E Kitchner

  4. Department of Medical Bioinformatics, Vanderbilt University School of Medicine, Nashville, TN, USA

    J Denny

  5. Department of Medicine, Vanderbilt University, Nashville, TN, USA

    J Denny, C Ingram, C M Shaffer, A Shah & P Weeke

  6. Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA

    J G Linneman

  7. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    M J McGeachie & S T Weiss

  8. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

    D M Roden

  9. Department of Cardiology, Copenhagen University Hospital, Gentofte, Denmark

    P Weeke

  10. School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA

    H Xu

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Naidoo, D., Wu, A., Brilliant, M. et al. A polymorphism in HLA-G modifies statin benefit in asthma. Pharmacogenomics J 15, 272–277 (2015). https://doi.org/10.1038/tpj.2014.55

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