Genetic determitants and gene-environment interactions in relation to the 10-year longitudinal development of lumbar bone mineral density in (young) adults

Ingrid Bakker, André G. Uitterlinden, Jos W.R. Twisk, Willem van Mechelen, Huibert A.P. Pols, Han C.G. Kemper

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Purpose. Genetic factors, as well as environmental factors (e.g. physical activity, nutritional intake, and body composition) are considered to influence the regulation of (young) adult bone quality. The association between lumbar bone mineral density (LBMD) and polymorphisms of three genes (i.e. VDR, ERα, COLIA1), as well as gene-environment interactions over a period of 10 years were investigated in (young) adult men and women. Basic procedures. The study was conducted in participants of the Amsterdam Growth and Health Longitudinal Study. Longitudinal analyses were performed in Dutch Caucasian males and females, including measurements at their mean ages of 27, 32 and 36 years. LBMD measurements were performed at the L2-L4 region by dual energy X-ray absorptiometry (DEXA). Polymorphism-containing regions were amplified from genomic DNA with the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Genotyping was performed for the Bsml, Apal, and Taql polymorphisms of the VDR, for the Pvull and Xbal polymorphisms of the ERα, and for the G-to-T polymorphism in the COLIA1 gene. Main findings. A positive allele-dose effect of the ERα haplotype PX on the development of (young) adult LBMD was found. Dietary calcium intake modified the relationship between VDR haplotypes and LBMD, and fat-free mass modified the relationship between COLIA1 polymorphisms and LBMD. Conclusions. An allele-dose relationship with LBMD during the third and fourth decades of life was detected for the PX haplotype allele of the VDR gene. Most Caucasian lumbar bones are likely to benefit from an increased calcium intake, and all will benefit from an increased fat-free mass.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalHuman Movement
Issue number2
Publication statusPublished - 2006


  • Adults
  • COLIA1
  • Estrogen receptor
  • Gene-environment interactions
  • Longitudinal
  • Lumbar bone mineral density
  • Polymorphisms
  • Vitamin D receptor

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