title: Association of Paraoxonase 1 (PON1) polymorphisms with osteoporotic fracture risk in postmenopausal Korean women.
abstract: There is increasing evidence of a biochemical link between lipid oxidation and bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density lipoprotein (LDL) and metabolizes biologically active phospholipids in oxidized LDLs. Here, we performed association analyses of genetic variation in PON1 to ascertain its contribution to osteoporotic fractures (OFs) and bone mineral density (BMD). We directly sequenced the PON1 gene in 24 Korean individuals and identified 26 sequence variants. A large population of Korean postmenopausal women (n=1,329) was then genotyped for eight selected PON1 polymorphisms. BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment, and the occurrence of non-vertebral fractures (i.e., wrist, hip, forearm, humerus, rib, and pelvis) was examined using self-reported data. Multivariate analyses showed that none of the polymorphisms was associated with BMD at either site. However, +5989A>G and +26080T>C polymorphisms were significantly associated with non-vertebral and vertebral fractures, respectively, after adjustment for covariates. Specifically, the minor allele of +5989A>G exerted a highly protective effect against non-vertebral fractures (OR=0.59, P=0.036), whereas the minor allele of +26080T>C was associated with increased susceptibility to vertebral fractures (OR=1.73, P=0.020). When the risk for any OFs (i.e., vertebral or non-vertebral) was considered, the statistical significance of both polymorphisms persisted (P=0.002-0.010). These results suggest that PON1 polymorphisms could be one of useful genetic markers for OF risk in postmenopausal women.
authors.affiliation: Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
authors.forename: Beom-Jun
authors.initials: BJ
authors.lastname: Kim
authors.forename: Shin-Yoon
authors.initials: SY
authors.lastname: Kim
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Cho
authors.forename: Bon-Jo
authors.initials: BJ
authors.lastname: Kim
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.forename: Eui-Kyun
authors.initials: EK
authors.lastname: Park
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Ghi Su
authors.initials: GS
authors.lastname: Kim
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Koh
mesh_terms: D000368:Aged; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015519:Bone Density; D005260:Female; D005787:Gene Frequency; D023061:Gene Order; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007723:Korea / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D043303:Aryldialkylphosphatase