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 Klein, Eric Orwoll, Siu L. Hui, Tatiana M. Foroud, Munro Peacock, Michael J. Econs

Research output: Contribution to journalArticle

61 Citations (Scopus)

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

Fingerprint

Spine
Genes
Single Nucleotide Polymorphism
Haplotypes
Osteoporosis
Arachidonate Lipoxygenases
Arachidonate 15-Lipoxygenase
Lipoxygenase
Femur Neck
Population

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Ichikawa, S., Koller, D. L., Johnson, M. L., Lai, D., Xuei, X., Edenberg, H. J., ... 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

Human ALOX12, but not ALOX15, is associated with BMD in white men and women. / Ichikawa, Shoji; Koller, Daniel L.; Johnson, Michelle L.; Lai, Dongbing; Xuei, Xiaoling; Edenberg, Howard J.; Klein, Robert; Orwoll, Eric; Hui, Siu L.; Foroud, Tatiana M.; Peacock, Munro; Econs, Michael J.

In: Journal of Bone and Mineral Research, Vol. 21, No. 4, 04.2006, p. 556-564.

Research output: Contribution to journalArticle

Ichikawa, S, Koller, DL, Johnson, ML, Lai, D, Xuei, X, Edenberg, HJ, Klein, R, Orwoll, E, Hui, SL, Foroud, TM, Peacock, M & Econs, MJ 2006, 'Human ALOX12, but not ALOX15, is associated with BMD in white men and women', Journal of Bone and Mineral Research, vol. 21, no. 4, pp. 556-564. https://doi.org/10.1359/jbmr.051212
Ichikawa, Shoji ; Koller, Daniel L. ; Johnson, Michelle L. ; Lai, Dongbing ; Xuei, Xiaoling ; Edenberg, Howard J. ; Klein, Robert ; Orwoll, Eric ; Hui, Siu L. ; Foroud, Tatiana M. ; Peacock, Munro ; Econs, Michael J. / Human ALOX12, but not ALOX15, is associated with BMD in white men and women. In: Journal of Bone and Mineral Research. 2006 ; Vol. 21, No. 4. pp. 556-564.
@article{3a2a54f6aebd498cb0c642682d2a3d5a,
title = "Human ALOX12, but not ALOX15, is associated with BMD in white men and women",
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.",
keywords = "Arachidonate lipoxygenase, BMD, Genetic association, Osteoporosis, Single nucleotide polymorphism",
author = "Shoji Ichikawa and Koller, {Daniel L.} and Johnson, {Michelle L.} and Dongbing Lai and Xiaoling Xuei and Edenberg, {Howard J.} and Robert Klein and Eric Orwoll and Hui, {Siu L.} and Foroud, {Tatiana M.} and Munro Peacock and Econs, {Michael J.}",
year = "2006",
month = "4",
doi = "10.1359/jbmr.051212",
language = "English (US)",
volume = "21",
pages = "556--564",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Human ALOX12, but not ALOX15, is associated with BMD in white men and women

AU - Ichikawa, Shoji

AU - Koller, Daniel L.

AU - Johnson, Michelle L.

AU - Lai, Dongbing

AU - Xuei, Xiaoling

AU - Edenberg, Howard J.

AU - Klein, Robert

AU - Orwoll, Eric

AU - Hui, Siu L.

AU - Foroud, Tatiana M.

AU - Peacock, Munro

AU - Econs, Michael J.

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

KW - Arachidonate lipoxygenase

KW - BMD

KW - Genetic association

KW - Osteoporosis

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=33645337659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645337659&partnerID=8YFLogxK

U2 - 10.1359/jbmr.051212

DO - 10.1359/jbmr.051212

M3 - Article

C2 - 16598376

AN - SCOPUS:33645337659

VL - 21

SP - 556

EP - 564

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 4

ER -