Association of polymorphisms of paraoxonase 1 and 2 genes, alone or in combination, with bone mineral density in community-dwelling Japanese.

Oxidative stress may affect cellular functions in various pathological conditions, including osteoporosis. Paraoxonase 1 confers antioxidant properties on high-density lipoprotein, with which it is associated, by reducing the accumulation of lipid peroxidation products. We have now examined whether the 584A-->G (Gln192Arg) and 172T-->A (Leu55Met) polymorphisms of the paraoxonase 1 gene and the 959G-->C (Cys311Ser) polymorphism of the paraoxonase 2 gene are associated with bone mineral density (BMD) in community-dwelling Japanese (1,087-1,094 women and 1,112-1,125 men). The subjects were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases. BMD for the lumbar spine and right femoral neck was measured by dual-energy X-ray absorptiometry. Genotypes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. The 584A-->G and 172T-->A polymorphisms of the paraoxonase 1 gene and the 959G-->C polymorphism of the paraoxonase 2 gene were associated with BMD for the lumbar spine or femoral neck in postmenopausal women, with the 584 GG, 172 TT, and 959 CC genotypes representing risk factors for reduced bone mass. None of these three polymorphisms was associated with BMD in premenopausal women or in men. Our results suggest that the paraoxonase 1 and 2 genes are candidate loci for reduced bone mass in postmenopausal Japanese women.