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.