Linked Life Data

16758144

Source:http://linkedlifedata.com/resource/pubmed/id/16758144

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-6-7
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0937-941X
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1078-85
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Association of PLOD1 polymorphisms with bone mineral density in a population-based study of women from the UK.
pubmed:affiliation
Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't