Human ALOX12, but not ALOX15, is associated with BMD in white men and women

Shoji Ichikawa, Daniel L. Koller, Michelle L. Johnson, Dongbing Lai, Xiaoling Xuei, Howard J. Edenberg, Robert F. Klein, Eric S. Orwoll, Siu L. Hui, Tatiana M. Foroud, Munro Peacock, Michael J. Econs

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The Alox15 gene was recently identified as a negative regulator of peak BMD in mice. Polymorphisms in human ALOX12, but not ALOX15, were significantly associated with spine BMD in white men and women, suggesting that ALOX12 may contribute to normal variation in BMD. Introduction: Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporosis is peak BMD, which is a highly heritable trait. Recently, the arachidonate 15-lipoxygenase (Alox15) gene was identified as a negative regulator of peak BMD in mice. Materials and Methods: To assess the contribution of lipoxygenase genes to normal BMD variation in healthy white men and women, we performed population- and family-based association studies of two arachidonate lipoxygenase genes: ALOX15, which is the human homolog of mouse Alox15, and ALOX12, which is functionally similar to Alox15. Single nucleotide polymorphisms (SNPs) distributed across the two genes were genotyped. BMD was measured at the femoral neck and lumbar spine in 411 men 18-61 years of age and 1291 premenopausal women 20-50 years of age. Results: Moderate evidence of association was found between spine BMD and six SNPs in the ALOX12 gene in both men and women (p = 0.0052-0.050). Furthermore, the most common SNP haplotype in ALOX12 showed evidence of significant association with high spine BMD in men (p = 0.0083), whereas the second most common haplotype was associated with high spine BMD in women (p = 0.0081). Conclusions: Polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD.

Original languageEnglish (US)
Pages (from-to)556-564
Number of pages9
JournalJournal of Bone and Mineral Research
Volume21
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Arachidonate lipoxygenase
  • BMD
  • Genetic association
  • Osteoporosis
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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    Ichikawa, S., Koller, D. L., Johnson, M. L., Lai, D., Xuei, X., Edenberg, H. J., Klein, R. F., Orwoll, E. S., Hui, S. L., Foroud, T. M., Peacock, M., & Econs, M. J. (2006). Human ALOX12, but not ALOX15, is associated with BMD in white men and women. Journal of Bone and Mineral Research, 21(4), 556-564. https://doi.org/10.1359/jbmr.051212