Gene polymorphisms,bone mineral density and bone mineral content in young children:the Iowa bone development study |
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Authors: | Email author" target="_blank">Marcia?C?WillingEmail author James?C?Torner Trudy?L?Burns Kathleen?F?Janz Teresa?Marshall Julie?Gilmore Sachi?P?Deschenes John?J?Warren Steven?M?Levy |
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Institution: | (1) Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;(2) Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA;(3) Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA;(4) Department of Health, Leisure and Sports Studies, College of Liberal Arts, University of Iowa, Iowa City, IA 52242, USA;(5) Department of Preventive and Community Dentistry, College of Dentistry, University of Iowa, Iowa City, IA 52242, USA;(6) Department of Pediatrics, 2609 JCP, Division of Medical Genetics, University of Iowa, Iowa City, IA 52242, USA |
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Abstract: | We examined the association of candidate gene polymorphisms with bone mineral density (BMD) and bone mineral content (BMC) in a cohort of 428 healthy non-Hispanic white children participating in the Iowa Bone Development Study, a longitudinal study of determinants of bone accrual in childhood. BMD and BMC measurements of the hip, spine and whole body were made using a Hologic 2000 Plus densitometer in 228 girls and 200 boys ages 4.5–6.5 years. Genotypes at 14 loci representing eight candidate genes type I collagen genes (COL1A1 and COL1A2), osteocalcin, osteonectin, osteopontin, vitamin D receptor (VDR), estrogen receptor (ER), androgen receptor (AR)] were determined. Gender-specific and gender-combined prediction models for bone measures that included age, weight, height (and gender) were developed using multiple linear regression analysis. COL1A2 and osteocalcin genotypes were identified as having the strongest and most consistent association with BMD/BMC measures. Osteonectin, osteopontin and VDR translation initiation site polymorphisms were associated with some individual bone measures, but none of the associations was as consistent as those identified for the COL1A2 and osteocalcin genes. No association was identified with COL1A1 (RsaI and Sp1), VDR (BsmI) and ER polymorphisms (PvuII, XbaI, TA) and BMD/BMC. However, we identified significant gene-by-gene interaction effects involving the ER and both VDR and osteocalcin, which were associated with BMD/BMC. Our data suggest that genetic variation at multiple genetic loci is important in bone accrual in children. Moreover, the combination of genotypes as several loci may be as important as a single genotype for determining BMD and BMC. |
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Keywords: | Bone Bone mineral density Children COL1A2 Genetic polymorphisms Osteocalcin |
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