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A differential association of ALOX15 polymorphisms with bone mineral density in pre- and post-menopausal women
Ching-Lung Cheung1, Vivian Chan, Annie W C Kung
1Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, SAR, China.
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.
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