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


BACKGROUND
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.


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.
Ichikawa
Shoji
S
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202-5121, USA.
Koller
Daniel L
DL
Johnson
Michelle L
ML
Lai
Dongbing
D
Xuei
Xiaoling
X
Edenberg
Howard J
HJ
Klein
Robert F
RF
Orwoll
Eric S
ES
Hui
Siu L
SL
Foroud
Tatiana M
TM
Peacock
Munro
M
Econs
Michael J
MJ
D000293:Adolescent; D000328:Adult; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D044465:White People / Q000235:genetics*
D001092:Arachidonate 12-Lipoxygenase; C476558:ALOX12 protein, human; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase