Exp Mol Med.
2011 Feb;43(2):71-81. 10.3858/emm.2011.43.2.009.
Association of Paraoxonase 1 (PON1) polymorphisms with osteoporotic fracture risk in postmenopausal Korean women
- Affiliations
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- 1Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
- 2Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu 700-412, Korea.
- 3The Center for Genome Science National Institute of Health, Seoul 122-701, Korea. leejy63@nih.go.kr
- 4Department of Pathology and Regenerative Medicine School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
- 5Division of Endocrinology and Metabolism Sanbon Medical Center, University of Wonkwang College of Medicine, Iksan 570-711, Korea.
- 6Department of Orthopedic Surgery School of Medicine, Kyungpook National University, Daegu 700-412, Korea.
- KMID: 1097264
- DOI: http://doi.org/10.3858/emm.2011.43.2.009
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.
Keyword
MeSH Terms
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Aged
Alleles
Aryldialkylphosphatase/*genetics
Bone Density
Female
Gene Frequency
Gene Order
Genetic Markers
Genetic Predisposition to Disease
Haplotypes
Humans
Korea/epidemiology
Linkage Disequilibrium
Male
Middle Aged
Molecular Typing
Osteoporotic Fractures/epidemiology/*genetics
*Polymorphism, Genetic
*Postmenopause
Risk Factors
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