Association of PLOD1 polymorphisms with bone mineral density in a population-based study of women from the UK

P. N. Tasker, H. MacDonald, W. D. Fraser, D. M. Reid, S. H. Ralston, Omar Al Bagha

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The PLOD1 gene is situated within a quantitative trait locus for regulation of bone mineral density (BMD) on chromosome 1p36 and is a strong functional candidate for the regulation of BMD and bone quality. PLOD1 encodes the enzyme procollagen-lysine, 2-oxoglutarate 5-dioxegenase (lysyl hydroxylase; EC 1.14.11.4), which catalyses the hydroxylation of lysine residues during the posttranslational modification of type I collagen, the major protein of bone. We investigated the role of PLOD1 as a genetic determinant of osteoporosis by studying two coding polymorphisms located in exon 3 of the PLOD1 gene in relation to BMD and bone loss in a population-based cohort of 678 Scottish women. We observed a significant association between lumbar spine (LS) BMD and a polymorphism at nucleotide 386 (G386A) of PLOD1, which results in an alanine-threonine amino acid change at codon 99 (A99T). Heterozygotes for G386A had significantly reduced LS-BMD when compared with the other genotype groups, and the difference remained significant after correcting for confounding factors. A similar association was observed between LS-BMD and a conservative polymorphism at position 385 (C385T), but this was in strong linkage disequilibrium (LD) with G386A. There was no evidence for an allele dose effect for either polymorphism, and the strongest association was observed in heterozygotes. No association was found between PLOD1 alleles and femoral-neck BMD or bone loss, but the hydroxylysylpyridinoline to lysylpyridinoline ratio was significantly increased in G386A heterozygotes compared with other genotype groups, suggesting a functional effect of this polymorphism on enzyme activity. Our findings show that heterozygosity for the A99T variant of PLOD1 is associated with reduced LS-BMD and an altered ratio of hydroxylysylpyridinoline to lysylpyridinoline. Whilst further studies will be required to confirm and extend these observations, our studies raise the possibility that A99T heterozygosity might affect lysyl hydroxylase function and regulate bone mass.

Original languageEnglish
Pages (from-to)1078-1085
Number of pages8
JournalOsteoporosis International
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Fingerprint

Bone Density
Population
2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine
Bone and Bones
Spine
Heterozygote
Lysine
Alleles
Genotype
Procollagen
Quantitative Trait Loci
Femur Neck
Linkage Disequilibrium
Enzymes
Threonine
Hydroxylation
Post Translational Protein Processing
Collagen Type I
Codon
Alanine

Keywords

  • Bone mineral density
  • PLOD1
  • Polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Association of PLOD1 polymorphisms with bone mineral density in a population-based study of women from the UK. / Tasker, P. N.; MacDonald, H.; Fraser, W. D.; Reid, D. M.; Ralston, S. H.; Al Bagha, Omar.

In: Osteoporosis International, Vol. 17, No. 7, 07.2006, p. 1078-1085.

Research output: Contribution to journalArticle

Tasker, P. N. ; MacDonald, H. ; Fraser, W. D. ; Reid, D. M. ; Ralston, S. H. ; Al Bagha, Omar. / Association of PLOD1 polymorphisms with bone mineral density in a population-based study of women from the UK. In: Osteoporosis International. 2006 ; Vol. 17, No. 7. pp. 1078-1085.
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