Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

Abstract

PurposeALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in young and elderly Swedish women. MethodsThree SNPs in ALOX12, five in ALOX15, one each in IL6 and PPARG were genotyped in the cohorts PEAK-25 (n=1061 women; all 25y) and OPRA (n=1044 women; all 75y). Bone mineral density (BMD) and quantitative ultrasound (QUS) were analyzed in both cohorts; trabecular bone score (TBS) in PEAK-25; bone loss, fracture incidence and serum C-reactive protein (CRP) were assessed in OPRA. ResultsIn the elderly women ALOX15 (rs2619112) was associated with CRP levels (p=0.004) and incident fracture of any type (p=0.014), although not with BMD or ultrasound. In young women, carrying the common T allele (ALOX 15 rs748694) was associated with lower QUS values (p=0.002–0.006). The IL6 SNP was associated with lower BMD in PEAK-25 (femoral neck p=0.034; hip p=0.012). TBS was not associated with variation in any gene. Variants in the ALOX12 and PPARγ were not associated with BMD in either cohort. ConclusionsThis study suggests that variation in inflammation related genes ALOX15 and IL6 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly, despite an observed association with CRP as a marker of inflammation and incident fracture.