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Polymorphisms of the interleukin-6 gene are associated with bone mineral density

Murray, R E; McGuigan, F LU ; Grant, S F; Reid, D M and Ralston, S H (1997) In Bone 21(1). p.89-92
Abstract

Genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone density, since it has stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. Here we studied the relationship between bone mineral density (BMD) and a polymorphic AT rich minisatellite repeat in the 3' flank of the IL-6 gene in a cohort of 200 women. Six length variants were identified (designated A-F), but four of these were rare such that the last majority of individuals fell into one of two common genotypes: F/F (58.5%) and C/F (27.5%). There was a... (More)

Genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone density, since it has stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. Here we studied the relationship between bone mineral density (BMD) and a polymorphic AT rich minisatellite repeat in the 3' flank of the IL-6 gene in a cohort of 200 women. Six length variants were identified (designated A-F), but four of these were rare such that the last majority of individuals fell into one of two common genotypes: F/F (58.5%) and C/F (27.5%). There was a significant relationship between IL-6 genotype and bone mass at the lumbar spine as determined by analysis of variance (p = 0.04) and a similar trend for bone mass at the femoral neck (p = 0.11). When BMD values were compared in the two common genotypes, we found that spine BMD values were significantly higher in the C/F genotype (mean +/- SEM = 0.94 +/- 0.04 g/cm2) as compared with the F/F genotype (0.81 +/- g/cm2; p = 0.012). A similar trend was seen for hip BMD values, but here, the difference failed to reach statistical significance (p = 0.06). Further analysis showed that genotype-specific effects on bone mass were observed in both premenopausal and postmenopausal women and did not increase with age, suggesting that the association between IL-6 polymorphisms and bone density may be mediated by an effect on peak bone mass, rather than rate of bone loss. We conclude that bone mass is associated with two common polymorphisms of the IL-6 gene. Although the mechanisms that underlie this association will require further research, our data suggest that polymorphic variation at the IL-6 gene locus may contribute to the genetic regulation of bone mass.

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published
keywords
Absorptiometry, Photon, Aged, Aged, 80 and over, Aging, Analysis of Variance, Bone Density, Cohort Studies, Female, Femur Neck, Genotype, Humans, Interleukin-6, Lumbar Vertebrae, Middle Aged, Polymorphism, Genetic, Postmenopause, Premenopause, Regression Analysis, Scotland, Journal Article, Research Support, Non-U.S. Gov't
in
Bone
volume
21
issue
1
pages
4 pages
publisher
Elsevier
external identifiers
  • scopus:0030857328
ISSN
8756-3282
language
English
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no
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d1c2bd87-2ed4-460c-9a57-5654c66cbdf5
date added to LUP
2018-01-02 11:13:16
date last changed
2018-10-03 11:22:26
@article{d1c2bd87-2ed4-460c-9a57-5654c66cbdf5,
  abstract     = {<p>Genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone density, since it has stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. Here we studied the relationship between bone mineral density (BMD) and a polymorphic AT rich minisatellite repeat in the 3' flank of the IL-6 gene in a cohort of 200 women. Six length variants were identified (designated A-F), but four of these were rare such that the last majority of individuals fell into one of two common genotypes: F/F (58.5%) and C/F (27.5%). There was a significant relationship between IL-6 genotype and bone mass at the lumbar spine as determined by analysis of variance (p = 0.04) and a similar trend for bone mass at the femoral neck (p = 0.11). When BMD values were compared in the two common genotypes, we found that spine BMD values were significantly higher in the C/F genotype (mean +/- SEM = 0.94 +/- 0.04 g/cm2) as compared with the F/F genotype (0.81 +/- g/cm2; p = 0.012). A similar trend was seen for hip BMD values, but here, the difference failed to reach statistical significance (p = 0.06). Further analysis showed that genotype-specific effects on bone mass were observed in both premenopausal and postmenopausal women and did not increase with age, suggesting that the association between IL-6 polymorphisms and bone density may be mediated by an effect on peak bone mass, rather than rate of bone loss. We conclude that bone mass is associated with two common polymorphisms of the IL-6 gene. Although the mechanisms that underlie this association will require further research, our data suggest that polymorphic variation at the IL-6 gene locus may contribute to the genetic regulation of bone mass.</p>},
  author       = {Murray, R E and McGuigan, F and Grant, S F and Reid, D M and Ralston, S H},
  issn         = {8756-3282},
  keyword      = {Absorptiometry, Photon,Aged,Aged, 80 and over,Aging,Analysis of Variance,Bone Density,Cohort Studies,Female,Femur Neck,Genotype,Humans,Interleukin-6,Lumbar Vertebrae,Middle Aged,Polymorphism, Genetic,Postmenopause,Premenopause,Regression Analysis,Scotland,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {1},
  pages        = {89--92},
  publisher    = {Elsevier},
  series       = {Bone},
  title        = {Polymorphisms of the interleukin-6 gene are associated with bone mineral density},
  volume       = {21},
  year         = {1997},
}