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Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men

Griet Vanbillemont UGent, Veerle Bogaert UGent, Dirk De Bacquer UGent, Bruno Lapauw UGent, Stefan Goemaere UGent, Kaatje Toye UGent, Kristel Van Steen UGent, Youri Taes UGent and Jean Kaufman UGent (2009) Clinical Endocrinology. 70(2). p.330-310
abstract
In men there is a large interindividual variation of SHBG levels and consequently of testosterone (T) and E-2 levels. Family and twin studies suggested a strong genetic contribution, besides metabolic and hormonal influences. The aim of this study was to examine the influence of a missense mutation in exon 8 (Asp327Asn) and a (TAAAA)(n)-repeat in the promoter region of the SHBG gene, on SHBG and sex steroid serum concentrations in a population of healthy men. SHBG and hormone levels were measured in 1485 men, contributed by three independent cohort studies and representing three different age groups (young, middle-aged and elderly men). The number of TAAAA-repeats was determined by fragment-analysis; carriers of the Asn(327)-allele were identified using restriction fragment length polymorphism analysis. In the different age groups, carriers of six TAAAA-repeats presented with higher SHBG (young 19%, middle-aged 20% and elderly 26%; P < 0.001) and T (young 9%, middle-aged 22% and elderly 21%; P < 0.05) levels compared to non-carriers. For free T, a modest increase was found for carriers in the middle-aged group, but not for the young and elderly group. E-2 and free E-2 did not differ between carriers and non-carriers in the different age-groups. The Asn(327)-allele was associated with higher mean SHBG (14.20%, P < 0.001) and T levels (7.33%; P = 0.01) in the middle-aged group only. Our findings show that and the (TAAAA)(n)-repeat and the Asp327Asn polymorphism contribute to the genetically determined interindividual variation in total serum T levels in healthy men through variation in SHBG concentrations.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
journal title
Clinical Endocrinology
Clin. Endocrinol.
volume
70
issue
2
pages
330 - 310
Web of Science type
Article
Web of Science id
000262636500019
JCR category
ENDOCRINOLOGY & METABOLISM
JCR impact factor
3.201 (2009)
JCR rank
41/104 (2009)
JCR quartile
2 (2009)
ISSN
0300-0664
DOI
10.1111/j.1365-2265.2008.03365.x
language
English
UGent publication?
yes
classification
A1
id
626461
handle
http://hdl.handle.net/1854/LU-626461
date created
2009-05-13 14:17:27
date last changed
2015-06-17 11:11:38
@article{626461,
  abstract     = {In men there is a large interindividual variation of SHBG levels and consequently of testosterone (T) and E-2 levels. Family and twin studies suggested a strong genetic contribution, besides metabolic and hormonal influences. The aim of this study was to examine the influence of a missense mutation in exon 8 (Asp327Asn) and a (TAAAA)(n)-repeat in the promoter region of the SHBG gene, on SHBG and sex steroid serum concentrations in a population of healthy men.

SHBG and hormone levels were measured in 1485 men, contributed by three independent cohort studies and representing three different age groups (young, middle-aged and elderly men). The number of TAAAA-repeats was determined by fragment-analysis; carriers of the Asn(327)-allele were identified using restriction fragment length polymorphism analysis.

In the different age groups, carriers of six TAAAA-repeats presented with higher SHBG (young 19\%, middle-aged 20\% and elderly 26\%; P {\textlangle} 0.001) and T (young 9\%, middle-aged 22\% and elderly 21\%; P {\textlangle} 0.05) levels compared to non-carriers. For free T, a modest increase was found for carriers in the middle-aged group, but not for the young and elderly group. E-2 and free E-2 did not differ between carriers and non-carriers in the different age-groups. The Asn(327)-allele was associated with higher mean SHBG (14.20\%, P {\textlangle} 0.001) and T levels (7.33\%; P = 0.01) in the middle-aged group only.

Our findings show that and the (TAAAA)(n)-repeat and the Asp327Asn polymorphism contribute to the genetically determined interindividual variation in total serum T levels in healthy men through variation in SHBG concentrations.},
  author       = {Vanbillemont, Griet and Bogaert, Veerle and De Bacquer, Dirk and Lapauw, Bruno and Goemaere, Stefan and Toye, Kaatje and Van Steen, Kristel and Taes, Youri and Kaufman, Jean},
  issn         = {0300-0664},
  journal      = {Clinical Endocrinology},
  language     = {eng},
  number       = {2},
  pages        = {330--310},
  title        = {Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men},
  url          = {http://dx.doi.org/10.1111/j.1365-2265.2008.03365.x},
  volume       = {70},
  year         = {2009},
}

Chicago
Vanbillemont, Griet, Veerle Bogaert, Dirk De Bacquer, Bruno Lapauw, Stefan Goemaere, Kaatje Toye, Kristel Van Steen, Youri Taes, and Jean Kaufman. 2009. “Polymorphisms of the SHBG Gene Contribute to the Interindividual Variation of Sex Steroid Hormone Blood Levels in Young, Middle-aged and Elderly Men.” Clinical Endocrinology 70 (2): 330–310.
APA
Vanbillemont, G., Bogaert, V., De Bacquer, D., Lapauw, B., Goemaere, S., Toye, K., Van Steen, K., et al. (2009). Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men. Clinical Endocrinology, 70(2), 330–310.
Vancouver
1.
Vanbillemont G, Bogaert V, De Bacquer D, Lapauw B, Goemaere S, Toye K, et al. Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men. Clinical Endocrinology. 2009;70(2):330–310.
MLA
Vanbillemont, Griet, Veerle Bogaert, Dirk De Bacquer, et al. “Polymorphisms of the SHBG Gene Contribute to the Interindividual Variation of Sex Steroid Hormone Blood Levels in Young, Middle-aged and Elderly Men.” Clinical Endocrinology 70.2 (2009): 330–310. Print.