Reference : Polymorphisms of the SHBG gene contribute to the interindividual variation of sex ste...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men
Vanbillemont, G. [> > > >]
Bogaert, V. [> > > >]
De Bacquer, D. [> > > >]
Lapauw, B. [> > > >]
Goemaere, S. [> > > >]
Toye, K. [> > > >]
Van Steen, Kristel mailto [Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique >]
Taes, Y. [> > > >]
Kaufman, J. M. [> > > >]
Clinical Endocrinology
Blackwell Publishing
Yes (verified by ORBi)
United Kingdom
[en] binding globulin shbg ; polycystic-ovary-syndrome ; additional carbohydrate chain ; bone-mineral density ; postmenopausal women ; serum testosterone ; plasma ; androgen ; repeat ; heritability
[en] 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.

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