A differential association of ALOX15 Polymorphisms with bone mineral density in pre- and post-menopausal women

Objective: The 12/15-lipoxygenase gene ALOX15 is reported to be a negative regulator of BMD in knockout mice. Nonetheless results are controversial as over-expression of ALOX15 protects against inflammation-related bone loss. The aim of the present study is to systematically study the relation of ALOX15 polymorphisms in BMD variation in southern Chinese women. Methods: Ten tag single nucleotide polymorphisms (SNP) were genotyped in 942 subjects with either low BMD (defined by a BMD Z score <=-1.28 at either the hip or spine) or high BMD (Z score >=+1). Single locus and haplotype associations were performed using logistic regression with adjustment of age, height and weight. Results: The variant 'G' allele of rs2619112 was associated with a reduced risk of low BMD at the femoral neck in pre-menopausal women ( OR = 0.442, p = 0.007) but an increased risk in postmenopausal women ( OR = 1.727, p = 0.042). Haplotype analysis revealed findings similar to the single locus tests. Conclusion: The variant alleles of rs2619112 and rs916055 and their haplotypes of ALOX15 are associated with high BMD in pre-menopausal women but low BMD in post-menopausal women. This suggests that ALOX15 is a dual modulator of BMD variation with opposing effects in pre- and post-menopausal women. Copyright (c) 2008 S. Karger AG, Basel.