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A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study

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Abstract

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development.

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Acknowledgements

This work is from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The Framingham Heart Study core examinations were supported by the National Heart, Lung, and Blood Institute’s (contract N01-HC-25195). Measurements of phenotypes were funded by the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute on Aging (grants R01 AR/AG 41398 and R01 AR050066). Genetic analyses were supported by NIH grants HL54776 and DK075030 and by the US Department of Agriculture Research Service (contracts 53-K06–5-10 and 58–1950-9–001). We gratefully acknowledge the Framingham Study members who participated in this study as well as the study coordinators, who contributed to the success of this work.

Disclosures

Dr. Douglas P. Kiel discloses a consultant/advisory role for Wyeth, Merck, Amgen, Novartis, Procter and Gamble, and Lilly and funding from Pfizer, Merck, Amgen, Novartis, and Hologic unrelated to the subject matter of this paper.

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Authors and Affiliations

  1. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Natalie E. Cusano & Douglas P. Kiel

  2. Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, PH 8 W-864, New York, NY, 10032, USA

    Natalie E. Cusano

  3. Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA, USA

    Douglas P. Kiel & David Karasik

  4. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    Serkalem Demissie, L. Adrienne Cupples & Qiong Gao

  5. National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, MA, USA

    Serkalem Demissie & L. Adrienne Cupples

  6. Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

    Dolores Corella, Kris Richardson, Nikos Yiannakouris & Jose M. Ordovas

  7. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, University of Valencia, Valencia, Spain

    Dolores Corella

  8. Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC), Madrid, Spain

    Jose M. Ordovas

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  1. Natalie E. Cusano
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Cusano, N.E., Kiel, D.P., Demissie, S. et al. A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study. Calcif Tissue Int 90, 96–107 (2012). https://doi.org/10.1007/s00223-011-9552-7

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