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 < or =-1.28 at either the hip or spine) or high BMD (Z score > or =+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 post-menopausal 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.