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Cited by 46Hormonal and reproductive studiesSexual Differentiation and DisordersGenetic Associations and Epidemiology

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

Vanbillemont, Griet, Bogaert, Veerle, De Bacquer, Dirk, Lapauw, Bruno, Goemaere, Stefan, Toye, Kaatje, Van Steen, Kristel, Taes, Youri +1 more·2009·Clinical Endocrinology
DOI 10.1111/j.1365-2265.2008.03365.x
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Abstract

Summary: Objective 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. Design 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. Results 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. Conclusions 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.

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Crossref · 10.1111/j.1365-2265.2008.03365.x

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  • Numerous estimating equations have been described, including bioavailable testosterone, free androgen index, and free testosterone index (Vermeulen method), with results suggesting high correlations with direct assays.

    “Numerous estimating equations have been described in the literature including bioavailable T (non-SHBG bound T), free androgen index (FAI; 100T/SHBG), and free T index (Vermeulen method), among others, with results suggesting high correlations to direct assays.”

    From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [105]

  • In the largest study evaluating predictive accuracy of free testosterone calculations, Sartorius and colleagues concluded that empirical methods (Ly, Sartorius) are most concordant, while other estimations (Vermeulen, Nanjee and Wheeler, Sodergard) overestimate the true value.

    “In the largest study evaluating predictive accuracy of fT calculations, Sartorius and colleagues concluded that empirical methods (Ly, Sartorius) of calculated fT are most concordant, with other estimations (Vermeulen, Nanjee and Wheeler, Sodergard) resulting in overestimation of the true value.”

    From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [105]

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Authors
Vanbillemont, G., Bogaert, V., De Bacquer, D., Lapauw, B., Goemaere, S., Toye, K., Van Steen, K., Taes, Y., & Kaufman, J.
Affiliations
Ghent University Hospital (BE)
Corresponding author
Vanbillemont, Griet
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2009-01-19
Volume
70
Issue
2
Pages
303-310
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/j.1365-2265.2008.03365.x
OpenAlex
W1774406863
Cited by
46
References
41
Citations by year
2025: 2 · 2024: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 5
FWCI
2.65
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Lirias (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
sex hormone-binding globulin, testosterone, estradiol, free testosterone, interindividual variability, healthy men, age differences
MeSH terms
Adult, Aged, Aged, 80 and over, Aging, Alleles, Androgens, DNA, Estrogens, Genotype, Humans, Male, Middle Aged, Polymorphism, Restriction Fragment Length, Sex Hormone-Binding Globulin, Testosterone, Body Mass Index, Microsatellite Repeats, Mutation, Missense, Polymorphism, Single Nucleotide

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