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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
Author(s) -
Vanbillemont Griet,
Bogaert Veerle,
De Bacquer Dirk,
Lapauw Bruno,
Goemaere Stefan,
Toye Kaatje,
Van Steen Kristel,
Taes Youri,
Kaufman JeanMarc
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03365.x
Subject(s) - sex hormone binding globulin , endocrinology , medicine , allele , missense mutation , biology , population , polymorphism (computer science) , testosterone (patch) , hormone , genetics , androgen , gene , mutation , environmental health
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.