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 language | English (US) |
|---|---|
| Pages (from-to) | 556-564 |
| Number of pages | 9 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 21 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2006 |
Fingerprint
Keywords
- Arachidonate lipoxygenase
- BMD
- Genetic association
- Osteoporosis
- Single nucleotide polymorphism
ASJC Scopus subject areas
- Surgery
Cite this
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 journal › Article
}
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 -