Source:http://linkedlifedata.com/resource/pubmed/id/12519862
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2003-1-9
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| pubmed:abstractText |
IL-6 is a pleiotropic cytokine that plays a critical role in bone resorption. We describe two allelic variants in the IL-6 promoter, -572 and -174 G-->C, that alone and in combination influence IL-6 activity in vitro and in vivo. The association of IL-6 -572 genotypes and -572/-174 G-->C haplotypes with serum C-reactive protein (CRP), serum and urinary C-terminal cross-linking of type I collagen (a marker of bone resorption), and osteocalcin (a marker of bone formation) was investigated in a cohort of healthy postmenopausal women (n = 495; mean age +/- SD, 72 +/- 5.7 yr). Among IL-6 -572 genotypes, CRP was 37% higher (P = 0.02) and urinary C-terminal cross-linking of type I collagen was 20% higher (P = 0.01) in the presence of the C allele, whereas serum osteocalcin was not different. IL-6 -572/-174 haplotypes (G/C, G/G, and C/G) were significantly associated with all biochemical markers, and additive effects of the two polymorphic loci were found. Thus, there was a significant increase in the level of CRP (up to +79%; P = 0.007) and bone resorption markers (up to +32%; P = 0.017) with a decreasing number (from four to one) of IL-6 protective alleles -572G and -174C. In addition, there was a trend for lower age-adjusted bone mineral density at the lumbar spine in subjects with less IL-6 protective alleles (up to -9.6%; P = 0.037; P = 0.08 after further adjustment for weight). In conclusion, we describe two functional polymorphisms in the IL-6 gene regulatory region associated with IL-6 activity in postmenopausal women, both systemically (CRP) and locally in bone. As such, IL-6 polymorphisms are able to influence the risk of osteoporosis as well as other chronic disorders involving IL-6 activity.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/C-Reactive Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0021-972X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
88
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
255-9
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:12519862-Aged,
pubmed-meshheading:12519862-Alleles,
pubmed-meshheading:12519862-Amino Acid Substitution,
pubmed-meshheading:12519862-Biological Markers,
pubmed-meshheading:12519862-Bone Density,
pubmed-meshheading:12519862-Bone Remodeling,
pubmed-meshheading:12519862-C-Reactive Protein,
pubmed-meshheading:12519862-Cysteine,
pubmed-meshheading:12519862-Female,
pubmed-meshheading:12519862-Gene Expression Regulation,
pubmed-meshheading:12519862-Genotype,
pubmed-meshheading:12519862-Glycine,
pubmed-meshheading:12519862-Haplotypes,
pubmed-meshheading:12519862-Humans,
pubmed-meshheading:12519862-Interleukin-6,
pubmed-meshheading:12519862-Osteoporosis, Postmenopausal,
pubmed-meshheading:12519862-Polymorphism, Genetic,
pubmed-meshheading:12519862-Promoter Regions, Genetic
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| pubmed:year |
2003
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| pubmed:articleTitle |
Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women.
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| pubmed:affiliation |
Division of Bone Diseases, World Health Organization Collaborating Center for Osteoporosis, University Hospital, 1211 Geneva, Switzerland. serge.ferrari@medecine.unige.ch
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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